{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:18:17Z","timestamp":1783955897558,"version":"3.55.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T00:00:00Z","timestamp":1642118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["335447717, SFB1328"],"award-info":[{"award-number":["335447717, SFB1328"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Antigen recognition by the T-cell receptor induces a cytosolic Ca<jats:sup>2+<\/jats:sup>signal that is crucial for T-cell function. The Ca<jats:sup>2+<\/jats:sup>channel TRPM2 (transient receptor potential cation channel subfamily M member 2) has been shown to facilitate influx of extracellular Ca<jats:sup>2+<\/jats:sup>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<jats:italic>in vitro<\/jats:italic>studies using T-cell lines and non-physiologic means of TRPM2 activation. Thus, the relevance of TRPM2-mediated Ca<jats:sup>2+<\/jats:sup>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<jats:italic>in vitro<\/jats:italic>,<jats:italic>Trpm2<\/jats:italic><jats:sup>-\/-<\/jats:sup>and WT CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells similarly upregulated the early activation markers NUR77, IRF4, and CD69. We also observed regular proliferation of<jats:italic>Trpm2<\/jats:italic><jats:sup>-\/-<\/jats:sup>CD8<jats:sup>+<\/jats:sup>T cells and unimpaired differentiation of CD4<jats:sup>+<\/jats:sup>T cells into Th1, Th17, and Treg cells under specific polarizing conditions.<jats:italic>In vivo<\/jats:italic>,<jats:italic>Trpm2<\/jats:italic><jats:sup>-\/-<\/jats:sup>and WT CD8<jats:sup>+<\/jats:sup>T cells showed equal specific responses to<jats:italic>Listeria monocytogenes<\/jats:italic>after infection of WT and<jats:italic>Trpm2<\/jats:italic><jats:sup>-\/-<\/jats:sup>mice and after transfer of WT and<jats:italic>Trpm2<\/jats:italic><jats:sup>-\/-<\/jats:sup>CD8<jats:sup>+<\/jats:sup>T cells into infected recipients. CD4<jats:sup>+<\/jats:sup>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<jats:italic>Trpm2<\/jats:italic><jats:sup>-\/-<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T cells. In conclusion, our results argue against a major function of TRPM2 in T-cell activation and differentiation.<\/jats:p>","DOI":"10.3389\/fimmu.2021.778916","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T05:57:20Z","timestamp":1642139840000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["TRPM2 Is Not Required for T-Cell Activation and Differentiation"],"prefix":"10.3389","volume":"12","author":[{"given":"Niels 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