TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell–mediated pathology
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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IL-23 is required to suppress IL-10 production.
“to suppress IL-10 production (McGeachy et al., 2007)”
From Distinct characteristics of hippocampal pathogenic th17 cells in a mouse model of depression (2018) · cites this paper as McGeachy et al., 2007
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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
- Licence
- www.springer.com/tdm (tdm)
- 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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