Romagnani, Andrea Vettore, Valentina Rezzonico-Jost, Tanja Hampe, Sarah Rottoli, Elsa Nadolni, Wiebke Perotti, Michela Meier, Melanie A. Hermanns, Constanze Geiger, Sheila Wennemuth, Gunther Recordati, Camilla Matsushita, Masayuki Muehlich, Susanne Proietti, Michele Chubanov, Vladimir Gudermann, Thomas Grassi, Fabio Zierler, Susanna 2017-12-04 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. application/pdf https://susi.usi.ch/global/documents/318985 https://localhost:5000/ark:/12658/srd1318985 https://susi.usi.ch/documents/318985/files/Romagnani_NC_2017.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-017-01960-z info:eu-repo/semantics/altIdentifier/ark/12658/srd1318985 info:eu-repo/semantics/openAccess CC BY Nature communications. - 2017, vol. 8, p. 1917 info:eu-repo/classification/udc/61 TRPM7 kinase activity is essential for T cell colonization and alloreactivity in the gut http://purl.org/coar/resource_type/c_6501