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; Samuel Huber

doi:10.1038/s41467-018-07581-4

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. LohseRichard A. Flavell, Christian Krebs, Jan Ake Gustafsson, Per Antonson, Maria Grazia Roncarolo, Eduardo J. Villablanca, Nicola Gagliani, Samuel Huber

Research output: Contribution to journal › Article

28 Scopus citations

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 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 Foxp3 ^neg 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.

Original language	English (US)
Article number	5457
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-07581-4
State	Published - Dec 1 2018

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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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, S. M., Sorini, C., Geginat, J., Fujio, K., Jacobs, T., Roesch, T., Izbicki, J. R., ... Huber, S. (2018). Molecular and functional heterogeneity of IL-10-producing CD4 ⁺ T cells Nature Communications, 9(1), [5457]. https://doi.org/10.1038/s41467-018-07581-4

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

In: Nature Communications, Vol. 9, No. 1, 5457, 01.12.2018.

Research output: Contribution to journal › Article

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 & Huber, S 2018, ' Molecular and functional heterogeneity of IL-10-producing CD4 ⁺ T cells ', Nature Communications, vol. 9, no. 1, 5457. https://doi.org/10.1038/s41467-018-07581-4

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. / Molecular and functional heterogeneity of IL-10-producing CD4 ⁺ T cells In: Nature Communications. 2018 ; Vol. 9, No. 1.

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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 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 Foxp3 neg 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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AU - Roncarolo, Maria Grazia

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