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Brockmann, Leonie; Soukou, Shiwa; Steglich, Babett; Czarnewski, Paulo; Zhao, Lilan; Wende, Sandra; Bedke, Tanja; Ergen, Can; Manthey, Carolin; Agalioti, Theodora; Geffken, Maria; Seiz, Oliver; Parigi, Sara M; Sorini, Chiara; Geginat, Jens; Fujio, Keishi; Jacobs, Thomas; Roesch, Thomas; Izbicki, Jacob R; Lohse, Ansgar W; Flavell, Richard A; Krebs, Christian; Gustafsson, Jan-Ake; Antonson, Per; Roncarolo, Maria Grazia; Villablanca, Eduardo J; Gagliani, Nicola; Huber, Samuel
Nature communications, 12/2018, Volume: 9, Issue: 1Journal Article
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 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 Foxp3 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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