TRPM7 kinase activity is essential for T cell colonization and alloreactivity in the gut. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Romagnani, Andrea; Vettore, Valentina; Rezzonico-Jost, Tanja; Hampe, Sarah; Rottoli, Elsa; Nadolni, Wiebke; Perotti, Michela; Meier, Melanie; Hermanns, Constanze; Geiger, Sheila; Wennemuth, Gunther; Recordati, Camilla; Matsushita, Masayuki; Muehlich, Susanne; Proietti, Michele; Chubanov, Vladimir; Gudermann, Thomas; Grassi, Fabio; Zierler, Susanna
• Is Part Of: Nature communications. Volume 8:Issue 1(2017)
• Page Start: 1
• Page End: 14
• Publication Date: 2017-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-017-01960-z
• Languages: English
• ISSNs: 2041-1723

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. Gut-homing and colonization of T cells are important for maintaining local immune homoeostasis and protective immunity. Here the authors show that the kinase activity of TRPM7 regulates Th17 differentiation and T cell alloreactivity in the gut by modulating SMAD2 activation and CD103 expression in T cells