TRPM7 kinase activity is essential for T cell colonization and alloreactivity in the gut.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29203869.
- Also identified by DOI 10.1038/s41467-017-01960-z and PMC identifier 5714948.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <sup>R/R</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.
Medical subject headings
- Graft vs Host Disease
- Intestines
- Lymphopoiesis
- T-Lymphocytes, Regulatory
- TRPM Cation Channels
- Th17 Cells