The DOI matches its Crossref record; 198 of the 198 references it cites were found in a registry or an index; none of the 215 sources its claims cite is checked for support yet.
The IL-17 Family of Cytokines in Health and Disease
Open accessAbstract
The interleukin 17 (IL-17) family of cytokines contains 6 structurally related cytokines, IL-17A through IL-17F. IL-17A, the prototypical member of this family, just passed the 25th anniversary of its discovery. While less is known about IL-17B-F, IL-17A (commonly known as IL-17) has received much attention for its pro-inflammatory role in autoimmune disease. Over the past decade, however, it has become clear that the functions of IL-17 are far more nuanced than simply turning on inflammation. Accumulating evidence indicates that IL-17 has important context- and tissue-dependent roles in maintaining health during response to injury, physiological stress and infection. Here, we discuss the functions of the IL-17 family, with a focus on the balance between the pathogenic and protective roles of IL-17 in cancer and autoimmune disease, including results of therapeutic blockade and novel aspects of IL-17 signal transduction regulation.
Overview
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Written from the paper’s full text.
TL;DR
This review surveys the IL-17 cytokine family, focusing on IL-17A and its context-dependent roles in host defense, tissue repair, autoimmunity, and cancer. It argues that IL-17 is not simply pro-inflammatory but can be protective or pathogenic depending on tissue, microbial context, and signaling environment.
Key findings
- IL-17A is the best-studied family member and is central to the IL-23–IL-17 axis, with therapeutic blockade showing strong efficacy in psoriasis: IL-17 and IL-23 inhibitors achieved complete PASI 100 responses in roughly 40–80% of patients.
- Therapeutic results diverge by disease: IL-17 blockade is effective in psoriatic arthritis and ankylosing spondylitis, but has limited benefit in rheumatoid arthritis and Crohn’s disease, where some patients experienced exacerbations or increased inflammation markers.
- IL-17 has protective roles at barrier surfaces and in injured tissues, including antifungal and antibacterial immunity, wound healing, and maintenance of intestinal epithelial tight junctions, while chronic or misplaced IL-17 responses drive tissue damage, bone erosion, fibrosis, and tumor-promoting inflammation.
- In colorectal cancer, IL-17 signatures associate with worse outcomes, and IL-17 may promote angiogenesis and resistance to anti-VEGF therapy; only about 8% of colon cancer patients have mismatch-repair deficiency/MSI and respond to anti-PD1, whereas MSS patients show elevated IL-17 and are largely unresponsive.
Methods
- Narrative review of the IL-17 family, with emphasis on IL-17A, synthesizing mechanistic, mouse-model, human genetic, and clinical trial literature.
- No primary experimental data, sample, or systematic search strategy are reported; the analysis is a conceptual synthesis of published findings.
- The review covers IL-17 structure and signaling, functions of IL-17B–F, IL-17A in barrier and non-barrier tissues, post-transcriptional regulation, and cancer pathogenesis.
Limitations
- The paper states that understanding of IL-17 biology remains in its infancy, especially regarding synergistic signaling, cytokine tuning, and microbial influences.
- It notes that IL-17B, IL-17C, and IL-17D are poorly studied, partly due to limited tools, and that orphan ligands and receptors remain in the family.
- Evident from the text: as a narrative review, it does not provide a systematic evidence appraisal, and its strong focus on IL-17A limits detailed coverage of other family members.
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Claims the paper makes
126 Not checked yet · 33 Own interpretation · 4 No basis given
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In the paper
“both the ligand and receptor were distinct in sequence from other known mammalian cytokines.”
§ The IL-17 family of cytokines in health and disease > Introduction
What the sources say
- Not checked yetcites Gaffen, 2011 source
- Not checked yetcites Yao et al., 1995a
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-17A (commonly known as IL-17) has received much attention for its pro-inflammatory role in autoimmune disease.”
§ The IL-17 family of cytokines in health and disease > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“the functions of IL-17 are far more nuanced than simply turning on inflammation.”
§ The IL-17 family of cytokines in health and disease > Abstract
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-17 has important context- and tissue-dependent roles in maintaining health during response to injury, physiological stress and infection.”
§ The IL-17 family of cytokines in health and disease > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“the IL-17 receptor family comprises a distinct subclass of receptors characterized by a shared cytoplasmic motif termed a “SEFIR”, which has a distant relationship with the TIR domain”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors
What the sources say
- Not checked yetcites Novatchkova et al., 2003 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The fact that IL-17 has been conserved in evolution demonstrates that its inflammatory activities have, on balance, been beneficial for human survival.”
§ The IL-17 family of cytokines in health and disease > Introduction
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In the paper
“IL-17 triggers activation of the canonical NF-κB cascade through IKK activation and IκBα degradation”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors
What the sources say
- Not checked yetcites Schwandner et al., 2000 source
- Not checked yetcites Yao et al., 1995a
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“these host-protective attributes can also be problematic, giving rise to immunopathology in autoimmunity, cancer or other inflammatory syndromes.”
§ The IL-17 family of cytokines in health and disease > Introduction
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In the paper
“Act1 has E3 Ubiquitin ligase activity”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors
What the sources say
- Not checked yetcites Liu et al., 2009 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Keratinocyte proliferation is driven by a non-canonical IL-17-mediated TRAF4:ERK5 activation pathway to promote tumorigenesis”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors
What the sources say
- Not checked yetcites Wu et al., 2015b
plaindirect- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 7
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In the paper
“present in species as early as jawless fish as well as Mollusca and sea urchins”
§ The IL-17 family of cytokines in health and disease > Introduction
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“this cytokine was elevated in human inflammatory or autoimmune diseases and was expressed in a non-canonical T helper cell population”
§ The IL-17 family of cytokines in health and disease > Introduction
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The so-called “IL-23-IL-17 axis” was found to function as a critical driver of autoimmune disease”
§ The IL-17 family of cytokines in health and disease > Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-17 was subsequently shown to be produced by other cell populations, such as CD8+ (Tc17) cells as well as various subsets of innate lymphocytes”
§ The IL-17 family of cytokines in health and disease > Introduction
What the sources say
- Not checked yetcites Cua and Tato, 2010
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The initial event in IL-17R signaling is recruitment of Act1 (aka CIKS), a multifunctional signaling protein that also contains a SEFIR domain necessary for IL-17R-Act1 association”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors
What the sources say
- Not checked yetcites Liu et al., 2011a
- Not checked yetcites Qian et al., 2007 source
- Not checked yetcites Sonder et al., 2011
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IκBζ is implicated in psoriasis both genetically and functionally”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“showed unexpected sequence homology with an open reading frame in Herpesvirus saimiri, a T cell tropic γ-herpesvirus, but not with other known cytokine families”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors
What the sources say
- Not checked yetcites Gaffen, 2011 source
- Not checked yetcites Yao et al., 1995a
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-17 also induces proliferative signaling in keratinocytes through Act1, a major facet of its impact in psoriasis and perhaps also explaining its involvement in skin tumorigenesis”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors
What the sources say
- Not checked yetcites Chiricozzi and Krueger, 2013
- Not checked yetcites Ha et al., 2014
- Not checked yetcites Langowski et al., 2006 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The Syk kinase was reported to bind to Act1 and TRAF6 and thus function upstream of NF-κB leading to expression of the chemokine CCL20”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors
What the sources say
- Not checked yetcites Wu et al., 2015c
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“TRAF6 also promotes activation of MAPK/AP1 pathways and the C/EBPβ and δ transcription factors”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-17B was originally found to increase during intestinal inflammation and to promote neutrophil migration upon intraperitoneal administration, suggesting a pro-inflammatory role”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Functions of IL-17 family members B through F
What the sources say
- Not checked yetcites Bie et al., 2017a
- Not checked yetcites Shi et al., 2000 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“NF-κB subsequently upregulates expression of IκBζ and Bcl3, noncanonical members of the NF-κB family that in turn promote expression of various IL-17-NF-κB driven pro-inflammatory and anti-microbial genes”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-17 was suggested to regulate NF-κB and CCL20 through CARMA2, encoded by CARD14”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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In the paper
“Mice lacking Act1 phenocopy Il17ra−/− mice, and rare humans with null mutations in ACT1 have identical phenotypes with respect to fungal susceptibility as those lacking IL17RA or IL17RC”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors
What the sources say
- Not checked yetcites Conti and Gaffen, 2015
- Not checked yetcites Li et al., 2017
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“During parasitic helminth infection, intestinal tuft cells produce large amounts of IL-25. This in turn promotes ILC2 cells to secretion IL-13, which programs epithelial crypt progenitors to differentiate toward goblet and tuft cells.”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Functions of IL-17 family members B through F
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-17C promotes anti-microbial protective responses and barrier maintenance in skin and intestine”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Functions of IL-17 family members B through F
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-25 was also shown to be produced by a subset of thymic epithelial cells that has chemosensory functions, similar to the intestinal tuft cells”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Functions of IL-17 family members B through F
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results indicate that IL-25 is a “barrier surface” cytokine and its production is largely regulated by environmental cues.”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Functions of IL-17 family members B through F
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-17F contributes to inflammatory responses and protection at barrier surfaces, as evidenced by heightened susceptibility to chronic mucocutaneous candidiasis in humans with an autosomal dominant IL17F deficiency”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Functions of IL-17 family members B through F
What the sources say
- Not checked yetcites Puel et al., 2011b
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“It is expressed in a wide variety of healthy tissues, and has been found to increase in tumors and during viral infection”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Functions of IL-17 family members B through F
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-17C is produced by epithelial cells rather than immune cells, hence acts as a rapid local autocrine response to epithelial injury.”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Functions of IL-17 family members B through F
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Early studies showed that IL-25 gene expression was elevated following Aspergillus and Nippostrongylus infection in the lung and gut, and that IL-25 promoted epithelial cell hyperplasia, increased mucus secretion, and airway hyperreactivity”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Functions of IL-17 family members B through F
What the sources say
- Not checked yetcites Owyang et al., 2006 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-17A, -AF and -F trigger qualitatively similar signaling pathways, however IL-17A homodimers induce a far more potent signal compared to IL-17F homodimers, with IL-17AF thought to be intermediate signaling strength”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Functions of IL-17 family members B through F
What the sources say
- Not checked yetcites Chang and Dong, 2007
- Not checked yetcites Wright et al., 2007 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-25 treatment elevated production of IL-13 and suppressed expression of IL-1, IL-6, and IL-23 by activated dendritic cells”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Functions of IL-17 family members B through F
What the sources say
- Not checked yetcites Kleinschek et al., 2007 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-17F and IL-17A are co-expressed on linked genes and are usually co-produced by Type 17 cells”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Functions of IL-17 family members B through F
What the sources say
- Not checked yetcites Akimzhanov et al., 2007 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“disease exacerbations observed in some patients treated with secukinumab (anti-IL-17) (Hueber et al., 2012), and increased serum C-reactive protein, an indicator of inflammation, in patients receiving brodalumab (anti-IL-17RA) (Targan et al., 2016).”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17A functions: Barrier surface protection and repair
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-17 induces IL-6 and G-CSF, cytokines that promote myeloid-driven innate inflammation”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17A functions: Barrier surface protection and repair
What the sources say
- Not checked yetcites Gaffen et al., 2014 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-17 production is increased during inflammatory bowel disease (Kleinschek et al., 2009), yet healthy intestine also contains significant populations of IL-17-producing cells.”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17A functions: Barrier surface protection and repair
What the sources say
- Not checked yetcites Kleinschek et al., 2009 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“mouse studies showed that colitis-associated epithelial injury and intestinal leakage can be exacerbated in absence of IL-17 signaling, and revealed that IL-17 serves a beneficial role in the intestinal epithelium by helping to maintain the epithelial tight-junction barrier during inflammation”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17A functions: Barrier surface protection and repair
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In psoriatic skin lesions, dysregulated IL-17 production or uncontrolled responses to IL-17 signaling promote pathogenic inflammation.”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17A functions: Barrier surface protection and repair
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“this pro-proliferative role likely contributes to the pathogenic effects of IL-17 in psoriasis, as well as potentially in skin cancer”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17A functions: Barrier surface protection and repair
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“the mechanical gum injury caused by chewing of hard foods increases gingival IL-17 levels, and increased IL-17 then contributes to periodontitis and bone erosion during aging”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17A functions: Barrier surface protection and repair
What the sources say
- Not checked yetcites Dutzan et al., 2017b
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hence the direct link between IL-23 and IL-17 observed in psoriasis does not appear to extend to inflammatory bowel disease, where IL-23 is likely driving an armory of additional effector molecules such that the specific protective functions of IL-17 in the injured gut apparently counterbalance its pathogenic potential.”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17A functions: Barrier surface protection and repair
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“oral IL-17 production is required to prevent outgrowth of gingivitis-causing bacteria in acute infections (Yu et al., 2007) and thus protect against bacterial inflammation-induced bone loss.”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17A functions: Barrier surface protection and repair
What the sources say
- Not checked yetcites Yu et al., 2007
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“IL-17 promotes glomerulonephritis following immune complex deposition in the kidney, and is thus thought to contribute to lupus renal disease”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Increased systemic IL-17 during pregnancy leads to development of autism-like behaviors in pup offspring (Choi et al., 2016), which can also be regulated by maternal microbiota (Kim et al., 2017).”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Th17 cells exacerbated depression-like symptoms in mice, and infiltrated the pre-frontal cortex and particularly hippocampus in depressed mice compared to controls”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Although joints are sterile tissues, dysregulated gut microbiota are found in autoimmune subjects, including those with rheumatoid arthritis (RA) (Scher et al., 2013), and have been demonstrated to contribute to arthritis susceptibility in mice”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Joints and barrier surfaces also have in common a relatively high exposure to mechanical stress during routine use, which may be analogous to oral tissues where mastication drives IL-17-induced damage”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
What the sources say
- Not checked yetcites Dutzan et al., 2017a
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“IL-17 blockade was effective in psoriatic arthritis (PsA) (McInnes et al., 2014; Mease and McInnes, 2016) as well as ankylosing spondylitis (AS)”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
What the sources say
- Not checked yetcites McInnes et al., 2014 source
- Not checked yetcites Mease and McInnes, 2016
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“IL-17 activates CNS-resident cells causing hyperexcitability of neurons (Siffrin et al., 2010), production of chemokines and cytokines by astrocytes and oligodendocytes and proliferation and ultimately death of oligodendrocyte precursors (Kang et al., 2013).”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“the predominance of IL-17 signaling occurs in none-hematopoietic cells expressing the heterodimeric IL-17RA:IL-17RC receptor.”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Balancing IL-17 effects in health and pathology at the level of signaling
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“IL-17 is protective when the kidney is injured by mechanical obstruction or systemic Candida albicans infection”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
What the sources say
- Not checked yetcites Ramani et al., 2016 source
- Not checked yetcites Ramani et al., 2018b
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings collectively indicate that IL-17 is a not simply a ‘catch-all’ master inflammatory factor, and highlights the need to consider concomitant tissue- and immune-specific factors that modulate the role of IL-17 during inflammation.”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
hedged- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It can be difficult to extrapolate these findings to humans, who have far more complex brain development and higher-order cognitive functioning than mice.”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“traumatic or ischemic brain injury patients frequently develop dysbiosis during hospitalization, which could alter immune responses in the inflamed brain”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
What the sources say
- Not checked yetcites Simon et al., 2017 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Following kidney injury, IL-17 promotes production of bradykinin by activating the kallikrein-kinin system in tubular epithelial cells (Ramani et al., 2018a), resulting in production of matrix metalloproteinases (MMPs) that reduce fibrosis”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
What the sources say
- Not checked yetcites Ramani et al., 2018a
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“In the healthy state, IL-17 directly influences the metabolic function of adipocytes, increasing expression of thermogenic enzymes and sensitivity to catecholamine”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
What the sources say
- Not checked yetcites Kohlgruber et al., 2018 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mice deficient in IL-17 and fed regular chow gain increased fat mass with age, corresponding to a role for IL-17 in regulating glucose homeostasis and inhibiting adipogenesis”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Phase II trials of secukinumab were reported to be successful in MS, but larger trials have yet to be initiated”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
What the sources say
- Not checked yetcites Patel and Kuchroo, 2015
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“proteins that control circadian rhythm in regulating IL-17 production by Th17 cells, including melatonin (Farez et al., 2015) and ERB-REV1a (Amir et al., 2018; Yu et al., 2013).”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Increased generation of IL-17-producing T cells during intestinal dysbiosis exacerbates central nervous system (CNS)-targeted autoimmune disease (Kumar et al., 2016) and impairs recovery following brain ischemia (stroke) (Benakis et al., 2016).”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“IL-17-deficient mice are susceptible to hypothermia, despite increased total body fat and accumulation of lipid droplets within adipocytes”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
What the sources say
- Not checked yetcites Kohlgruber et al., 2018 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, MMP production is a characteristic response to IL-17, suggesting that regulation of wound healing and fibrotic scarring could be a more general function of IL-17 following injury.”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“IL-17 promotes neuroinflammation and neurodegeneration in rodent models of multiple sclerosis and stroke”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 functions in non-barrier stressed tissues
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“However, Regnase-1 and Roquins are thought to target different transcripts by virtue of distinct subcellular localization: Regnase-1 targets actively-translating transcripts during acute inflammation by associating with polysomes, whereas Roquins tend to target translationally inactive mRNAs”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 induces RNA-binding proteins to tune signaling outcomes
What the sources say
- Not checked yetcites Mino et al., 2015 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“In mice, segmented filamentous bacteria (SFB) form direct physical contact with mouse intestinal epithelial cells and thereby promote intestinal IL-17 signature genes”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Roles of IL-17 in pathogenesis of cancer
What the sources say
- Not checked yetcites Ivanov et al., 2009 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The IL-17-driven pathway that controls RNA stability is initiated by phosphorylation of Act1 by Ikki (IKKe), directing its association to TRAF2 and TRAF5. and mobilizing multiple RBPs”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 induces RNA-binding proteins to tune signaling outcomes
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Interestingly, Regnase-1 and Roquins regulate IL-17 production by regulating Th17 differentiation”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 induces RNA-binding proteins to tune signaling outcomes
What the sources say
- Not checked yetcites Jeltsch et al., 2014 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one. The quote only partly states this claim.
None of the sources cited for this claim have been checked yet.
In the paper
“that degrades IL-17-induced mRNA transcripts, thus acting as a feedback inhibitor”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 induces RNA-binding proteins to tune signaling outcomes
What the sources say
- Not checked yetcites Akira, 2013 source
- Not checked yetcites Fu and Blackshear, 2017
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“IL-17 induces both positive and negative regulators of its own signaling pathways, resulting in complex feedback loops that can amplify or attenuate the inflammatory response”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Balancing IL-17 effects in health and pathology at the level of signaling
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“For many tumor types, particularly at mucosal barriers, gene signatures of Th1 cells (IFNG, STAT1, TBX21) and CD8+ cytotoxic T cells (PRF1, GZMB) are linked to better overall and relapse-free patient survival, whereas Th17 cell signatures (RORC, IL17, IL23, STAT3) correspond to worse patient outcomes”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Roles of IL-17 in pathogenesis of cancer
What the sources say
- Not checked yetcites Tosolini et al., 2011 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition to synergizing with strong NF-κB activators such as TNFα, lipopolysaccharide (LPS), IL-1β and lymphotoxin, IL-17 cooperates with IFNγ (activator of STAT1), IL-13 (STAT6), TGFβ (SMADs), fibroblast growth factor (FGF)2 (Ras:Raf) and a Candida albicans-derived pore-forming toxin from Candida albicans (c-Fos)”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Balancing IL-17 effects in health and pathology at the level of signaling
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Regnase-1 binds similar RNA sites to the RBPs Roquin-1 and Roquin-2, which also restrict IL-17 signaling by degrading target genes”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > IL-17 induces RNA-binding proteins to tune signaling outcomes
What the sources say
- Not checked yetcites Jeltsch et al., 2014 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nevertheless, these results suggest that the composition of the gut microbiome likely alters the balance between favorable Th1 and CD8+ cytotoxic T cell response versus unfavorable tolerogenic or Th17 immune responses and could thus mediate patient response to immunotherapy.”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Roles of IL-17 in pathogenesis of cancer
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Anti-IL-17 was administered and cleared the psoriasis, but unfortunately the cancer progressed”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Concluding remarks
What the sources say
- Not checked yetcites Esfahani and Miller, 2017
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Remarkably, many of these patients are highly responsive to checkpoint blockade treatment (Diaz and Le, 2015; Le et al., 2017; Le et al., 2015) where the tumor infiltrating CD8+ cytotoxic T cells can be reactivated by anti-PD1 antagonists to effectively eradicate tumors.”
§ The IL-17 family of cytokines in health and disease > Structure and signaling of IL-17 family cytokines and receptors > Roles of IL-17 in pathogenesis of cancer
What the sources say
- Not checked yetcites Diaz and Le, 2015 source
- Not checked yetcites Le et al., 2017
- Not checked yetcites Le et al., 2015
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
IL-17 is the signature cytokine of a distinct CD4+ T helper subset, Th17 cells, which express RORγt and are activated by IL-23.
“IL-17 is the signature cytokine of a distinct CD4+ T helper subset, T helper 17 (Th17) cells, which are characterized by expression of the “master” transcription factor RORγt and activated by the IL-12-family cytokine, IL-23.”
The paper relies on this without support.
Findings from mouse models of IL-17 biology are informative about human IL-17 biology and disease.
“Mouse models indicate that IL-17B signaling through IL-17RB promotes survival, proliferation and migration of cancer cells in mouse models”
The paper relies on this without support.
IL-17A is the most strongly implicated IL-17 family member in human health and disease, justifying the review's focus on it.
“this review will focus on IL-17A as it has been most strongly implicated in human health and disease.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In addition, IL-17 stimulates neutrophils to eliminate extracellular pathogens (McGeachy et al., 2019).”
From Iron in infection and immunity (2020) · cites this paper as McGeachy et al., 2019
Experimental — accuracy not yet measured
Citations
Cites
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500596 · Cited by 9,377
Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade
Le, D. T., Durham, J. N., Smith, K. N., Wang, H., Bartlett, B. R., Aulakh, L. K., Lu, S., Kemberling, H., Wilt, C., Luber, B. S., et al. (2017) · Science · doi:10.1126/science.aan6733 · Cited by 6,645
Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors
Routy, B., Le Chatelier, E., Derosa, L., Duong, C. P. M., Alou, M. T., Daillère, R., Fluckiger, A., Messaoudene, M., Rauber, C., Roberti, M. P., et al. (2018) · Science · doi:10.1126/science.aan3706 · Cited by 5,671
Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients
Gopalakrishnan, V., Spencer, C. N., Nezi, L., Reuben, A., Andrews, M. C., Karpinets, T. V., Prieto, P. A., Vicente, D., Hoffman, K., Wei, S. C., et al. (2018) · Science · doi:10.1126/science.aan4236 · Cited by 4,812 · cited 2×
“Indeed, recent studies provided direct evidence that the microbiome community can influence responsiveness to checkpoint blockade therapy (Gopalakrishnan et al., 2018; Routy et al., 2018).”
BackgroundHarrington, L. E., Hatton, R. D., Mangan, P. R., Turner, H., Murphy, T. L., Murphy, K. M., & Weaver, C. T. (2005) · Nature Immunology · doi:10.1038/ni1254 · Cited by 4,742
Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.033 · Cited by 4,554
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Metadata
- Authors
- McGeachy, M. J., Cua, D. J., & Gaffen, S. L.
- Affiliations
- University of Pittsburgh (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Corresponding author
- McGeachy, Mandy J.
- Cua, Daniel J.
- Gaffen, Sarah L.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 50
- Issue
- 4
- Pages
- 892-906
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC6474359
- OpenAlex
- W2939946042
- Semantic Scholar
- ac9595c105d61927109ca0a3aaf531e8f062ad1c
- Cited by
- 1,443
- References
- 198
- Citations by year
- 2026: 180 · 2025: 239 · 2024: 266 · 2023: 196 · 2022: 247 · 2021: 165 · 2020: 122 · 2019: 28
- FWCI
- 12.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (AI110822, DE0225500, AI107825)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IL-17 family, IL-17A, inflammatory cytokines, autoimmune disease, cancer, IL-17 inhibition, infection, injury response, physiological stress
- MeSH terms
- Animals, Autoimmune Diseases, Brain, Gene Expression Regulation, T-Lymphocytes, Helper-Inducer, Humans, Infections, Inflammation, Neoplasms, Stress, Physiological, Wounds and Injuries, Signal Transduction, Cytokines, RNA-Binding Proteins, Interleukin-17, Mice, Receptors, Interleukin-17, Molecular Targeted Therapy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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