Cited by 1,520Psoriasis: Treatment and PathogenesisT-cell and B-cell ImmunologyIL-33, ST2, and ILC Pathways

TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell–mediated pathology

McGeachy, Mandy J, Bak-Jensen, Kristian S, Chen, Yi, Tato, Cristina M, Blumenschein, Wendy, McClanahan, Terrill, Cua, Daniel J·2007·Nature Immunology

Abstract

Studies have shown that transforming growth factor-beta (TGF-beta) and interleukin 6 (IL-6) are required for the lineage commitment of pathogenic IL-17-producing T helper cells (T(H)-17 cells). Unexpectedly, here we found that stimulation of myelin-reactive T cells with TGF-beta plus IL-6 completely abrogated their pathogenic function despite upregulation of IL-17 production. Cells stimulated with TGF-beta plus IL-6 were present in the spleen as well as the central nervous system, but they failed to upregulate the proinflammatory chemokines crucial for central nervous system inflammation. In addition, these cells produced IL-10, which has potent anti-inflammatory activities. In contrast, stimulation with IL-23 promoted expression of IL-17 and proinflammatory chemokines but not IL-10. Hence, TGF-beta and IL-6 'drive' initial lineage commitment but also 'restrain' the pathogenic potential of T(H)-17 cells. Our findings suggest that full acquisition of pathogenic function by effector T(H)-17 cells is mediated by IL-23 rather than by TGF-beta and IL-6.

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Crossref · 10.1038/ni1539

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Authors
McGeachy, M. J., Bak-Jensen, K. S., Chen, Y., Tato, C. M., Blumenschein, W., McClanahan, T., & Cua, D. J.
Corresponding author
Cua, Daniel J
Venue
Nature Immunology
Published
2007-11-11
Volume
8
Issue
12
Pages
1390-1397
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
OpenAlex
W2092975931
Cited by
1,520
References
7
Citations by year
2026: 32 · 2025: 42 · 2024: 50 · 2023: 74 · 2022: 61 · 2021: 76 · 2020: 65 · 2019: 75 · 2018: 57 · 2017: 73 · 2016: 84 · 2015: 91 · 2014: 88 · 2013: 103 · 2012: 102
FWCI
41.80
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
Keywords
TGF-beta, interleukin-6, IL-17, IL-10, Th17 cells, T cell lineage commitment, myelin-specific T cells, IL-23, neuroinflammation, chemokines, multiple sclerosis, autoimmunity
MeSH terms
Animals, Cell Differentiation, T-Lymphocytes, Helper-Inducer, T-Lymphocytes, Interleukin-6, Transforming Growth Factor beta, Interleukin-10, Cell Lineage, Interleukin-17, Mice

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