The DOI matches its Crossref record; 279 of the 280 references it cites were found in a registry or an index.
Pleiotropy and Specificity: Insights from the Interleukin 6 Family of Cytokines
Open accessAbstract
Since the molecular cloning of interleukin-6 (IL-6) in 1986, many other cytokines have been found to share the same signal transducer, gp130, in their receptor complexes. Thus, the IL-6 family of cytokines now consists of ten members. Although some of the family members' functions are redundant as a result of the expression of gp130, there are also functional distinctions between members. The mechanisms that determine functional redundancies and distinctions are not completely understood. Yet, research has clarified the role of IL-6 family cytokines in autoimmune diseases and has led to effective therapies that target them. Here, we review the IL-6 family of cytokines in autoimmune diseases, with a particular focus on the prototypical member IL-6, from the viewpoints of their structure, signaling, and biological features and discuss possible mechanisms of their functional pleiotropy.
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In the citing paper
“Binding of IL-6 to IL-6RA and gp130 leads to activation of JAK/ STAT3 and, to a lesser extent, YAP.23”
From Kupffer-cell-derived IL-6 is repurposed for hepatocyte dedifferentiation via activating progenitor genes from injury-specific enhancers (2023) · cites this paper as [23]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Proper transduction of the IL-6 signal requires IL-6 receptor IL-6RA and co-receptor gp130.23”
From Kupffer-cell-derived IL-6 is repurposed for hepatocyte dedifferentiation via activating progenitor genes from injury-specific enhancers (2023) · cites this paper as [23]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“As IL-6/STAT3 signaling is mainly involved in the proinflammatory response, 23 it was unexpected that it controlled cell identity conversion in liver injury.”
From Kupffer-cell-derived IL-6 is repurposed for hepatocyte dedifferentiation via activating progenitor genes from injury-specific enhancers (2023) · cites this paper as [23]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“IL-6 is a prototypical member of the IL-6 family of cytokines, which is composed of 10 members including IL-6, IL-11, IL-27, oncostatin M (OSM), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), cardiotrophin 1 (CT-1), cardiotrophin-like cytokine factor 1 (CLCF1), IL-35 and IL-39 (33).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [33]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The IL-6R is composed of an IL-6-binding receptor molecule (IL-6Rα) and a signal transducer, gp130, which is shared among the IL-6 family of cytokines (Fig. 1A) (33).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [33]
Experimental — accuracy not yet measured
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In the citing paper
“IL-6 transcription is induced by a variety of stimuli, such as Toll-like receptor (TLR) ligands, IL-1, TNFα, reactive oxygen species (ROS) and zinc (Zn) and also depends on epigenetic regulation (33, 82, 84–86).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [33]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Indeed, this mode plays crucial roles in chronic inflammation (33, 96).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [33]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“For IL-6 activity, the expression of both IL-6Rα and gp130 on the cell surface is required, which limits the number of target cells on which IL-6 acts to lymphocytes, myeloid cells and hepatocytes (33).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [33]
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In the citing paper
“Furthermore, ADAM17 increases sIL-6Rα, which activates STAT3 through gp130 on a variety of non-immune cells including fibroblasts, endothelial cells and epithelial cells (33, 96).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [33]
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Citations
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Self-citationBlastocyst implantation depends on maternal expression of leukaemia inhibitory factor
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The cytokine storm and COVID-19
Hu, B., Huang, S., & Yin, L. (2021) · Journal of Medical Virology · doi:10.1002/jmv.26232 · Cited by 1,655
IL-6 in inflammation, autoimmunity and cancer
Hirano, T. (2021) · International Immunology · doi:10.1093/intimm/dxaa078 · Cited by 1,453
“IL-6 is a prototypical member of the IL-6 family of cytokines, which is composed of 10 members including IL-6, IL-11, IL-27, oncostatin M (OSM), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), cardiotrophin 1 (CT-1), cardiotrophin-like cytokine factor 1 (CLCF1), IL-35 and IL-39 (33).”
BackgroundInfluentialSelf-citationCOVID-19: a new virus, but a familiar receptor and cytokine release syndrome
Hirano, T., & Murakami, M. (2020) · Immunity · doi:10.1016/j.immuni.2020.04.003 · Cited by 772
Self-citationThe cytokine network involved in the host immune response to periodontitis
Pan, W., Wang, Q., & Chen, Q. (2019) · International Journal of Oral Science · doi:10.1038/s41368-019-0064-z · Cited by 740
How COVID-19 induces cytokine storm with high mortality
Hojyo, S., Uchida, M., Tanaka, K., Hasebe, R., Tanaka, Y., Murakami, M., & Hirano, T. (2020) · Inflammation and Regeneration · doi:10.1186/s41232-020-00146-3 · Cited by 663
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Metadata
- Authors
- Murakami, M., Kamimura, D., & Hirano, T.
- Affiliations
- Hokkaido University (JP)
- Corresponding author
- Hirano, Toshio
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 50
- Issue
- 4
- Pages
- 812-831
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2936183454
- Cited by
- 533
- References
- 280
- Citations by year
- 2026: 52 · 2025: 70 · 2024: 76 · 2023: 69 · 2022: 90 · 2021: 98 · 2020: 63 · 2019: 15
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- QST-Repository (National Institutes for Quantum and Radiological Science and Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- JSPS-KAKENHI
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- interleukin-6, IL-6 family cytokines, gp130, cytokine signaling, functional redundancy, pleiotropy, specificity, autoimmune disease, cytokine structure, therapeutic targeting
- MeSH terms
- Interleukin-6 Inhibitors, Animals, Autoimmune Diseases, Gene Expression Regulation, Multigene Family, Inflammation, Structure-Activity Relationship, Signal Transduction, Interleukin-6, Cytokines, Receptors, Cytokine, Receptors, Interleukin-6, Protein Subunits, Mice, Genetic Pleiotropy
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