Facoltà di scienze biomediche

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

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

In: Nature communications, 2017, vol. 8, p. 1917

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 ... More

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    Summary
    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.