TRPM7 kinase activity is essential for T cell colonization and alloreactivity in the gut
Romagnani A, Vettore V, Rezzonico-Jost T, Hampe S, Rottoli E, Nadolni W, Perotti M, Meier MA, Hermanns C, Geiger S, Wennemuth G, Recordati C, Matsushita M, Muehlich S, Proietti M, Chubanov V, Gudermann T, Grassi F, Zierler S (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 8
Article Number: 1917
Journal Issue: 1
DOI: 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.
Involved external institutions
Institute for Research in Biomedicine
Switzerland (CH)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
Università degli studi di Milano
Italy (IT)
Universitätsklinikum Essen
Germany (DE)
University of the Ryukyus / 琉球大学
Japan (JP)
Switzerland (CH)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
Università degli studi di Milano
Italy (IT)
Universitätsklinikum Essen
Germany (DE)
University of the Ryukyus / 琉球大学
Japan (JP)
How to cite
APA:
Romagnani, A., Vettore, V., Rezzonico-Jost, T., Hampe, S., Rottoli, E., Nadolni, W.,... Zierler, S. (2017). TRPM7 kinase activity is essential for T cell colonization and alloreactivity in the gut. Nature Communications, 8(1). https://doi.org/10.1038/s41467-017-01960-z
MLA:
Romagnani, Andrea, et al. "TRPM7 kinase activity is essential for T cell colonization and alloreactivity in the gut." Nature Communications 8.1 (2017).
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