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

A Romagnani, V Vettore, T Rezzonico-Jost… - Nature …, 2017 - nature.com
A Romagnani, V Vettore, T Rezzonico-Jost, S Hampe, E Rottoli, W Nadolni, M Perotti…
Nature communications, 2017nature.com
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 …
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 (Trpm7R/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.
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