1. Molecular and functional heterogeneity of IL-10-producing CD4 + T cells.
- Author
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Brockmann L, Soukou S, Steglich B, Czarnewski P, Zhao L, Wende S, Bedke T, Ergen C, Manthey C, Agalioti T, Geffken M, Seiz O, Parigi SM, Sorini C, Geginat J, Fujio K, Jacobs T, Roesch T, Izbicki JR, Lohse AW, Flavell RA, Krebs C, Gustafsson JA, Antonson P, Roncarolo MG, Villablanca EJ, Gagliani N, and Huber S
- Subjects
- Animals, Humans, Mice, Inbred C57BL, Single-Cell Analysis, Transcriptome, CD4-Positive T-Lymphocytes metabolism, Inflammatory Bowel Diseases immunology, Interleukin-10 metabolism
- Abstract
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 Foxp3neg 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.- Published
- 2018
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