期刊
NATURE IMMUNOLOGY
卷 19, 期 10, 页码 1126-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41590-018-0200-5
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资金
- European Research Council [323183]
- Swiss National Science Foundation [149475, 170213]
- US National Institutes of Health [NS076410]
- Helmut Horten Foundation
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P01NS076410, R01NS030843] Funding Source: NIH RePORTER
Different types of effector and memory T lymphocytes are induced and maintained in protective or pathological immune responses. Here we characterized two human CD4(+) T(H)17 helper cell subsets that, in the recently activated state, could be distinguished on the basis of their expression of the anti-inflammatory cytokine IL-10. IL-10(+) T(H)17 cells upregulated a variety of genes encoding immunoregulatory molecules, as well as genes whose expression is characteristic of tissue-resident T cells. In contrast, IL-10-T(H)17 cells maintained a pro-inflammatory gene-expression profile and upregulated the expression of homing receptors that guide recirculation from tissues to blood. Expression of the transcription factor c-MAF was selectively upregulated in IL-10(+) T(H)17 cells, and it was bound to a large set of enhancer-like regions and modulated the immunoregulatory and tissue-residency program. Our results identify c-MAF as a relevant factor that drives two highly divergent post-activation fates of human T(H)17 cells and provide a framework with which to investigate the role of these cells in physiology and immunopathology.
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