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

Media type: E-Article
Title: TRPM7 kinase activity is essential for T cell colonization and alloreactivity in the gut
Contributor: 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
Published: Springer Science and Business Media LLC, 2017
Published in: Nature Communications, 8 (2017) 1
Language: English
DOI: 10.1038/s41467-017-01960-z
ISSN: 2041-1723
Origination:
Footnote:
Description: <jats:title>Abstract</jats:title><jats:p>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 (<jats:italic>Trpm7</jats:italic><jats:sup><jats:italic>R/R</jats:italic></jats:sup>) 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.</jats:p>
Access State: Open Access

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