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Mucosal Immunol. 2017 Nov;10(6):1431-1442. doi: 10.1038/mi.2017.5. Epub 2017 Feb 15.

TH17 cells express ST2 and are controlled by the alarmin IL-33 in the small intestine.

Author information

1
Charité Universitätsmedizin-Berlin, Berlin, Germany.
2
Deutsches Rheuma Forschungszentrum (DRFZ), a Leibniz Institute, Berlin, Germany.
3
Experimental Immunology, Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Berlin, Germany.
4
Medizinische Mikrobiologie, Immunologie und Hygiene der TU München, München, Germany.
5
Department of Biology, Institute of Molecular Health Sciences, RNAi and Genome Integrity, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland.
6
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
7
I. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
8
German Center for Infection Research (DZIF), Munich, Munich, Germany.
9
Immunobiology Department, Yale School of Medicine, Connecticut, New Haven, USA.

Abstract

TH17 cells are major drivers of inflammation and involved in several autoimmune diseases. Tissue inflammation is a beneficial host response to infection, but it can also contribute to autoimmunity. The crosstalk between a tissue and the immune system during an inflammatory response is key for preserving tissue integrity and restoring physiological processes. However, how the inflamed tissue regulates the magnitude of an immune response by controlling pro-inflammatory T cells is not well characterized so far. Here we show that TH17 cells accumulating in the small intestine upon inflammation express the IL-33 receptor (ST2) and intestinal epithelial cells (IEC) are the main source of the alarmin interleukin-33 (IL-33). We show that pro-inflammatory TH17 cells acquire a regulatory phenotype with immunosuppressive properties in response to IL-33. Absence of ST2 signaling promotes the secretion of pro-inflammatory cytokines by TH17 cells and dampens the secretion of IL-10. Our results provide new insights into the mechanisms by which IEC, via IL-33/ST2 axis, may control pro-inflammatory TH17 cells in the small intestine to sustain homeostasis.

PMID:
28198366
DOI:
10.1038/mi.2017.5
[Indexed for MEDLINE]

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