期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-07581-4
关键词
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资金
- Robert A Welch Foundation [E-0004]
- DFG [SFB1192, SFB841, GA 2441/3-1, HU 1714/10-1]
- ERC [715271]
- Stiftung Experimentelle Biomedizin
- Heisenberg Professorship
- European Research Council (ERC) [715271] Funding Source: European Research Council (ERC)
IL-10 is a prototypical anti-inflammatory cytokine, which is fundamental to the maintenance of immune homeostasis, especially in the intestine. There is an assumption that cells producing IL-10 have an immunoregulatory function. However, here we report that IL-10-producing CD4(+) T cells are phenotypically and functionally heterogeneous. By combining single cell transcriptome and functional analyses, we identified a subpopulation of IL-10-producing Foxp3(neg) CD4(+) T cells that displays regulatory activity unlike other IL-10-producing CD4(+) T cells, which are unexpectedly pro-inflammatory. The combinatorial expression of co-inhibitory receptors is sufficient to discriminate IL-10-producing CD4(+) T cells with regulatory function from others and to identify them across different tissues and disease models in mice and humans. These regulatory IL-10-producing Foxp3neg CD4(+) T cells have a unique transcriptional program, which goes beyond the regulation of IL-10 expression. Finally, we found that patients with Inflammatory Bowel Disease demonstrate a deficiency in this specific regulatory T-cell subpopulation.
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