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

Leonie Brockmann, Shiwa Soukou, Babett Steglich, Paulo Czarnewski, Lilan Zhao, Sandra Wende, Tanja Bedke, Can Ergen, Carolin Manthey, Theodora Agalioti, Maria Geffken, Oliver Seiz, Sara M. Parigi, Chiara Sorini, Jens Geginat, Keishi Fujio, Thomas Jacobs, Thomas Roesch, Jacob R. Izbicki, Ansgar W. Lohse, Richard A. Flavell, Christian Krebs, Jan-Ake Gustafsson, Per Antonson, Maria Grazia Roncarolo, Eduardo J. Villablanca, Nicola Gagliani () and Samuel Huber ()
Additional contact information
Leonie Brockmann: University Medical Center Hamburg-Eppendorf
Shiwa Soukou: University Medical Center Hamburg-Eppendorf
Babett Steglich: University Medical Center Hamburg-Eppendorf
Paulo Czarnewski: Karolinska Institute and University Hospital
Lilan Zhao: University Medical Center Hamburg-Eppendorf
Sandra Wende: University Medical Center Hamburg-Eppendorf
Tanja Bedke: University Medical Center Hamburg-Eppendorf
Can Ergen: University Medical Center Hamburg-Eppendorf
Carolin Manthey: University Medical Center Hamburg-Eppendorf
Theodora Agalioti: University Medical Center Hamburg-Eppendorf
Maria Geffken: Institute of Transfusion Medicine, University Medical Center Hamburg-Eppendorf
Oliver Seiz: University Medical Center Hamburg-Eppendorf
Sara M. Parigi: Karolinska Institute and University Hospital
Chiara Sorini: Karolinska Institute and University Hospital
Jens Geginat: INGM-National Institute of Molecular Genetics “Romeo ed Enrica Invernizzi”
Keishi Fujio: The University of Tokyo
Thomas Jacobs: Bernhard-Nocht-Institute of Tropical Medicine
Thomas Roesch: University Medical Center Hamburg-Eppendorf
Jacob R. Izbicki: University Medical Center Hamburg-Eppendorf
Ansgar W. Lohse: University Medical Center Hamburg-Eppendorf
Richard A. Flavell: Yale University
Christian Krebs: University Medical Center Hamburg-Eppendorf
Jan-Ake Gustafsson: Karolinska Institutet
Per Antonson: Karolinska Institutet
Maria Grazia Roncarolo: ISCBRM, Stanford School of Medicine
Eduardo J. Villablanca: Karolinska Institute and University Hospital
Nicola Gagliani: University Medical Center Hamburg-Eppendorf
Samuel Huber: University Medical Center Hamburg-Eppendorf

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07581-4

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DOI: 10.1038/s41467-018-07581-4

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