Data di Pubblicazione:
2017
Citazione:
TRPM7 kinase activity is essential for T cell colonization and alloreactivity in the gut / A. Romagnani, V. Vettore, T. Rezzonico-Jost, S. Hampe, E. Rottoli, W. Nadolni, M. Perotti, M.A. Meier, C. Hermanns, S. Geiger, G. Wennemuth, C. Recordati, M. Matsushita, S. Muehlich, M. Proietti, V. Chubanov, T. Gudermann, F. Grassi, S. Zierler. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 8:1(2017 Dec), pp. 1917.1-1917.14. [10.1038/s41467-017-01960-z]
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Animals; Antigens, CD; Cell Differentiation; Genes, MHC Class II; Graft vs Host Disease; Integrin alpha Chains; Intestines; Lymphopoiesis; Mice; Mutation; Smad2 Protein; T-Lymphocytes; T-Lymphocytes, Regulatory; TRPM Cation Channels; Th17 Cells; Transforming Growth Factor beta
Elenco autori:
A. Romagnani, V. Vettore, T. Rezzonico-Jost, S. Hampe, E. Rottoli, W. Nadolni, M. Perotti, M.A. Meier, C. Hermanns, S. Geiger, G. Wennemuth, C. Recordati, M. Matsushita, S. Muehlich, M. Proietti, V. Chubanov, T. Gudermann, F. Grassi, S. Zierler
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