P14 - The kinase-coupled TRPM7 channel as key regulator of immune system homeostasis
The channel kinase TRPM7 has been implicated in the regulation of cellular Mg2+ levels, motility, and cell cycle. Genetic inactivation of TRPM7 in mice results in profound immune phenotypes such as impaired thymopoiesis, dysregulated chemokine and cytokine expression and allergic hypersensitivity. These findings together with our preliminary data suggest that TRPM7 channel and kinase activities play a critical role in inflammation and pro-inflammatory diseases. To test this hypothesis we will study phenotypic presentations of TRPM7 kinase deficient mice and ex vivo derived immune cells in a broadly used DSS-induced pro-inflammatory colitis model.
Figure. Potential role of TRPM7 signaling in gut immune responses. We hypothesize that TRPM7 regulates pro-inflammatory responses, by promoting M1 maturation and TH17 polarization, triggered by pro-inflammatory cytokines and ATP. Similarly, depletion of TRPM7 might influence M2a differentiation and Treg polarization in response to anti-inflammatory signals. TRPM7 kinase function might be important for immunological reactivity of cells. If TRPM7 kinase is compromised, Mg2+ deficiency further exaggerates immune responses. Thus, TRPM7 channel and kinase activity might be crucial for signaling in immune cells.