AUTHOR=Lory Niels C. , Nawrocki Mikolaj , Corazza Martina , Schmid Joanna , Schumacher Valéa , Bedke Tanja , Menzel Stephan , Koch-Nolte Friedrich , Guse Andreas H. , Huber Samuel , Mittrücker Hans-Willi TITLE=TRPM2 Is Not Required for T-Cell Activation and Differentiation JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.778916 DOI=10.3389/fimmu.2021.778916 ISSN=1664-3224 ABSTRACT=

Antigen recognition by the T-cell receptor induces a cytosolic Ca²⁺ signal that is crucial for T-cell function. The Ca²⁺ channel TRPM2 (transient receptor potential cation channel subfamily M member 2) has been shown to facilitate influx of extracellular Ca²⁺ through the plasma membrane of T cells. Therefore, it was suggested that TRPM2 is involved in T-cell activation and differentiation. However, these results are largely derived from in vitro studies using T-cell lines and non-physiologic means of TRPM2 activation. Thus, the relevance of TRPM2-mediated Ca²⁺ signaling in T cells remains unclear. Here, we use TRPM2-deficient mice to investigate the function of TRPM2 in T-cell activation and differentiation. In response to TCR stimulation in vitro, Trpm2^-/- and WT CD4⁺ and CD8⁺ T cells similarly upregulated the early activation markers NUR77, IRF4, and CD69. We also observed regular proliferation of Trpm2^-/- CD8⁺ T cells and unimpaired differentiation of CD4⁺ T cells into Th1, Th17, and Treg cells under specific polarizing conditions. In vivo, Trpm2^-/- and WT CD8⁺ T cells showed equal specific responses to Listeria monocytogenes after infection of WT and Trpm2^-/- mice and after transfer of WT and Trpm2^-/- CD8⁺ T cells into infected recipients. CD4⁺ T-cell responses were investigated in the model of anti-CD3 mAb-induced intestinal inflammation, which allows analysis of Th1, Th17, Treg, and Tr1-cell differentiation. Here again, we detected similar responses of WT and Trpm2^-/- CD4⁺ T cells. In conclusion, our results argue against a major function of TRPM2 in T-cell activation and differentiation.