TRPM7 kinase activity plays an essential role in T cell colonization of small intestine epithelium

The gene transient receptor potential-melastatin-like 7 (Trpm7) encodes a protein that functions as ion channel and serine/threonine kinase. TRPM7 is widely expressed in cells of both innate and adaptive immune system. Tissue-specific deletion of Trpm7 in the T cell lineage was shown to affect thymopoiesis, indicating that the channel and/or the associated kinase are important in T cell development.  To specifically address the role of TRPM7 kinase activity in T cells, we used mice carrying an inactive TRPM7 kinase domain (TKI). In contrast to conditional Trpm7-/- mice, TKI mice are characterized by normal T cell development in the thymus, indicating that the kinase activity is not responsible for the thymic phenotype observed previously. Moreover, T cells in spleen and peripheral lymph nodes are normally distributed. However, TKI mice show hypotrophic Peyer’s patches and reduced amount of secreted IgA in the small intestine. Notably, intraepithelial T cells (IEL) are particularly affected by lack of TRPM7 kinase activity and CD103 expression is strongly reduced. The lack of IEL in TKI mice results in significantly reduced expression of MHCII in intestinal epithelial cells. We found that the defect of IEL retention within small intestine epithelium is T cell intrinsic. In fact, adoptive transfer of lymphopenic host with naïve CD4 cells from TKI mice did not result in CD103 upregulation, reconstitution of IEL pool and MHCII expression in intestinal epithelial cells. Our results suggest that TRPM7 kinase activity plays a fundamental role in T cell colonization and patrolling of gut epithelium.