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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; [...]

Molecular and functional heterogeneity of IL-10-producing CD4+ T cells

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  • Media type: E-Article
  • Title: Molecular and functional heterogeneity of IL-10-producing CD4+ T cells
  • Contributor: 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; [...]
  • imprint: Springer Science and Business Media LLC, 2018
  • Published in: Nature Communications, 9 (2018) 1
  • Language: English
  • DOI: 10.1038/s41467-018-07581-4
  • ISSN: 2041-1723
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>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<jats:sup>+</jats:sup> T cells are phenotypically and functionally heterogeneous. By combining single cell transcriptome and functional analyses, we identified a subpopulation of IL-10-producing Foxp3<jats:sup>neg</jats:sup> CD4<jats:sup>+</jats:sup> T cells that displays regulatory activity unlike other IL-10-producing CD4<jats:sup>+</jats:sup> T cells, which are unexpectedly pro-inflammatory. The combinatorial expression of co-inhibitory receptors is sufficient to discriminate IL-10-producing CD4<jats:sup>+</jats:sup> 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<jats:sup>neg</jats:sup> CD4<jats:sup>+</jats:sup> 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.</jats:p>
  • Access State: Open Access