TRPM7 kinase activity is essential for T cell colonization and alloreactivity in the gut
- Romagnani, Andrea Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Graduate School for Cellular and Biomedical Sciences, University of Bern, c/o Theodor Kocher Institute, Freiestrasse 1, P.O. Box 938, CH-3000 Bern 9, Switzerland
- Vettore, Valentina Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians Universität München, Goethestrasse 33, 80336 Munich, Germany
- Rezzonico-Jost, Tanja Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
- Hampe, Sarah Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians Universität München, Goethestrasse 33, 80336 Munich, Germany
- Rottoli, Elsa Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Università degli Studi di Milano, Via G.B. Viotti 3/5, 20133 Milan, Italy
- Nadolni, Wiebke Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians Universität München, Goethestrasse 33, 80336 Munich, Germany
- Perotti, Michela Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
- Meier, Melanie A. Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians Universität München, Goethestrasse 33, 80336 Munich, Germany
- Hermanns, Constanze Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians Universität München, Goethestrasse 33, 80336 Munich, Germany
- Geiger, Sheila Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians Universität München, Goethestrasse 33, 80336 Munich, Germany
- Wennemuth, Gunther Institute for Anatomy, Universitätsklinikum Essen, Hufelandstrasse 55, 45147 Essen, Germany
- Recordati, Camilla Filarete Foundation, Viale Ortles 22/4, 20139 Milan, Italy
- Matsushita, Masayuki Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Okinawa 903-0215, Japan
- Muehlich, Susanne Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians Universität München, Goethestrasse 33, 80336 Munich, Germany
- Proietti, Michele Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Center for Chronic Immunodeficiency, Universitätsklinikum Freiburg, Breisacher Street 115, 79106 Freiburg, Germany
- Chubanov, Vladimir Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians Universität München, Goethestrasse 33, 80336 Munich, Germany
- Gudermann, Thomas Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians Universität München, Goethestrasse 33, 80336 Munich, Germany
- Grassi, Fabio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Università degli Studi di Milano, Via G.B. Viotti 3/5, 20133 Milan, Italy - Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Via Francesco Sforza, 35-20122 Milan, Italy
- Zierler, Susanna Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians Universität München, Goethestrasse 33, 80336 Munich, Germany
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04.12.2017
Published in:
- Nature communications. - 2017, vol. 8, p. 1917
English
The melastatin-like transient-receptor-potential-7 protein (TRPM7), harbouring a cation channel and a serine/threonine kinase, has been implicated in thymopoiesis and cytokine expression. Here we show, by analysing TRPM7 kinase-dead mutant (Trpm7 R/R) mice, that the enzymatic activity of the receptor is not essential for thymopoiesis, but is required for CD103 transcription and gut-homing of intra-epithelial lymphocytes. Defective T cell gut colonization reduces MHCII expression in intestinal epithelial cells. Mechanistically, TRPM7 kinase activity controls TGF-β-induced CD103 expression and pro-inflammatory T helper 17, but not regulatory T, cell differentiation by modulating SMAD2. Notably, we find that the TRPM7 kinase activity promotes gut colonization by alloreactive T cells in acute graft-versus-host disease. Thus, our results unravel a function of TRPM7 kinase in T cell activity and suggest a therapeutic potential of kinase inhibitors in averting acute graft-versus-host disease.
- Language
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- English
- Classification
- Medicine
- License
- License undefined
- Identifiers
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- RERO DOC 327179
- DOI 10.1038/s41467-017-01960-z
- ARK ark:/12658/srd1318985
- Persistent URL
- https://n2t.net/ark:/12658/srd1318985
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