TRPM7 kinase activity is essential for T cell colonization and alloreactivity in the gut

Andrea Romagnani, Valentina Vettore, Tanja Rezzonico-Jost, Sarah Hampe, Elsa Rottoli, Wiebke Nadolni, Michela Perotti, Melanie A. Meier, Constanze Hermanns, Sheila Geiger, Gunther Wennemuth, Camilla Recordati, Masayuki Matsushita, Susanne Muehlich, Michele Proietti, Vladimir Chubanov, Thomas Gudermann, Fabio Grassi () and Susanna Zierler ()
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Andrea Romagnani: Università della Svizzera Italiana
Valentina Vettore: Ludwig-Maximilians Universität München
Tanja Rezzonico-Jost: Università della Svizzera Italiana
Sarah Hampe: Ludwig-Maximilians Universität München
Elsa Rottoli: Università degli Studi di Milano
Wiebke Nadolni: Ludwig-Maximilians Universität München
Michela Perotti: Università della Svizzera Italiana
Melanie A. Meier: Ludwig-Maximilians Universität München
Constanze Hermanns: Ludwig-Maximilians Universität München
Sheila Geiger: Ludwig-Maximilians Universität München
Gunther Wennemuth: Universitätsklinikum Essen
Camilla Recordati: Filarete Foundation
Masayuki Matsushita: University of the Ryukyus
Susanne Muehlich: Ludwig-Maximilians Universität München
Michele Proietti: Università della Svizzera Italiana
Vladimir Chubanov: Ludwig-Maximilians Universität München
Thomas Gudermann: Ludwig-Maximilians Universität München
Fabio Grassi: Università della Svizzera Italiana
Susanna Zierler: Ludwig-Maximilians Universität München

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-01960-z

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