Th17: An Effector CD4 T Cell Lineage with Regulatory T Cell Ties

Weaver, Casey T.; Harrington, Laurie E.; Mangan, Paul R.; Gavrieli, Maya; Murphy, Kenneth M.

doi:10.1016/j.immuni.2006.06.002

Cited by 1,422T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisIL-33, ST2, and ILC Pathways

Th17: An Effector CD4 T Cell Lineage with Regulatory T Cell Ties

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Weaver, Casey T., Harrington, Laurie E., Mangan, Paul R., Gavrieli, Maya, Murphy, Kenneth M.·2006·Immunity

DOI 10.1016/j.immuni.2006.06.002

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Abstract

The naive CD4 T cell is a multipotential precursor with defined antigen recognition specificity but substantial plasticity for development down distinct effector or regulatory lineages, contingent upon signals from cells of the innate immune system. The range of identified effector CD4 T cell lineages has recently expanded with description of an IL-17-producing subset, called Th17, which develops via cytokine signals distinct from, and antagonized by, products of the Th1 and Th2 lineages. Remarkably, Th17 development depends on the pleiotropic cytokine TGF-beta, which is also linked to regulatory T cell development and function, providing a unique mechanism for matching CD4 T cell effector and regulatory lineage specification. Here, we review Th17 lineage development, emphasizing similarities and differences with established effector and regulatory T cell developmental programs that have important implications for immune regulation, immune pathogenesis, and host defense.

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The requirement for paracrine IL-6 in Th17 cells draws a parallel between Th17 cells and Treg cells.
“draws a further parallel between Th17 cells and Treg cells (62).”
From T H 17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity (2020) · cites this paper as [62]
Th17 cells have well-established pathological actions in other diseases.
“The well-established pathological actions of Th17 cells in other diseases (45–47)”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [47]
IL-17 is produced by Th17 cells, CD8+ T cells, and innate lymphocytes such as γδ T cells, NK cells, and NKT cells.
“IL-17 is not only the master cytokine of Th17 cells but is also produced by CD8+ T cells and innate lymphocytes, such as γδ T cells, NK cells, and NKT cells.73”
From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [73]

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Inflammation Directs Memory Precursor and Short-Lived Effector CD8+ T Cell Fates via the Graded Expression of T-bet Transcription Factor
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Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction
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Immune adaptations that maintain homeostasis with the intestinal microbiota
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Immunology of asthma and chronic obstructive pulmonary disease
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mTOR differentially regulates effector and regulatory T cell lineage commitment
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Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17
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Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages
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Late Developmental Plasticity in the T Helper 17 Lineage
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Inflammasomes and Their Roles in Health and Disease
Lamkanfi, M., & Dixit, V. M. (2012) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101011-155745 · Cited by 935 · see citing works
TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1
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Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3
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Regulation of Immune Responses by mTOR
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IL-17 can promote tumor growth through an IL-6–Stat3 signaling pathway
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Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments
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Innate and Adaptive Interleukin-22 Protects Mice from Inflammatory Bowel Disease
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The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease
Afzali, B., Lombardi, G., Lechler, R. I., & Lord, G. M. (2007) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2007.03356.x · Cited by 762 · see citing works
Regulation of inflammatory responses by IL-17F
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Th17 Cell Differentiation: The Long and Winding Road
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The development of inflammatory TH-17 cells requires interferon-regulatory factor 4
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CD27 is a thymic determinant of the balance between interferon-γ- and interleukin 17–producing γδ T cell subsets
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IL-21 Is Produced by Th17 Cells and Drives IL-17 Production in a STAT3-dependent Manner
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Interleukin-22 but Not Interleukin-17 Provides Protection to Hepatocytes during Acute Liver Inflammation
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TH17 cells in tumour immunity and immunotherapy
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Prostate cancer and inflammation: the evidence
Sfanos, K. S., & Marzo, A. M. D. (2011) · Histopathology · doi:10.1111/j.1365-2559.2011.04033.x · Cited by 614 · see citing works
Mast Cell Function
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Preferential Generation of Follicular B Helper T Cells from Foxp3 + T Cells in Gut Peyer's Patches
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IL-23 plays a key role in Helicobacter hepaticus –induced T cell–dependent colitis
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Preconditioning and tolerance against cerebral ischaemia: from experimental strategies to clinical use
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The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation
Chang, H.-C., Sehra, S., Goswami, R., Yao, W., Yu, Q., Stritesky, G. L., Jabeen, R., McKinley, C., Ahyi, A.-N., Han, L., et al. (2010) · Nature Immunology · doi:10.1038/ni.1867 · Cited by 577 · see citing works
Osteoimmunology: Interactions of the Bone and Immune System
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Stat3 and Stat4 Direct Development of IL-17-Secreting Th Cells
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The Genetics of Inflammatory Bowel Disease
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Regulatory T cells expressing interleukin 10 develop from Foxp3+ and Foxp3− precursor cells in the absence of interleukin 10
Maynard, C. L., Harrington, L. E., Janowski, K. M., Oliver, J. R., Zindl, C. L., Rudensky, A. Y., & Weaver, C. T. (2007) · Nature Immunology · doi:10.1038/ni1504 · Cited by 599 · see citing works
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Sphingosine 1-phosphate receptors in health and disease: Mechanistic insights from gene deletion studies and reverse pharmacology
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Regulation of immunological homeostasis in the respiratory tract
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Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis
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A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells
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Contextual Regulation of Inflammation: A Duet by Transforming Growth Factor-β and Interleukin-10
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When worlds collide: Th17 and Treg cells in cancer and autoimmunity
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Authors: Weaver, C. T., Harrington, L. E., Mangan, P. R., Gavrieli, M., & Murphy, K. M.
Affiliations: University of Alabama at Birmingham (US)
Howard Hughes Medical Institute (US)
Corresponding author: Weaver, Casey T.
ORCID: Weaver, Casey T.
Harrington, Laurie E.
Murphy, Kenneth M.
Venue: Immunity
Publisher: Elsevier BV
Published: 2006-06
Volume: 24
Issue: 6
Pages: 677-688
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2006.06.002
OpenAlex: W2131678280
Cited by: 1,422
References: 105
Citations by year: 2026: 15 · 2025: 12 · 2024: 18 · 2023: 43 · 2022: 27 · 2021: 42 · 2020: 32 · 2019: 32 · 2018: 35 · 2017: 44 · 2016: 53 · 2015: 59 · 2014: 64 · 2013: 84 · 2012: 87
FWCI: 13.36
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2603 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Allergy and Infectious Diseases (AI-35783, AI57956, R01AI057956)
National Institute of Diabetes and Digestive and Kidney Diseases (DK64400, R24DK064400)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
Keywords: Th17 cells, CD4+ T cell differentiation, regulatory T cells, TGF-beta, IL-17, immune regulation, immune pathogenesis, host defense
MeSH terms: Animals, Autoimmune Diseases, Cell Differentiation, CD4-Positive T-Lymphocytes, Cell Lineage, Interleukin-17, T-Lymphocytes, Regulatory, Mice

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Th17: An Effector CD4 T Cell Lineage with Regulatory T Cell Ties

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