TRPM2 Is Not Required for T-Cell Activation and Differentiation.

Antigen recognition by the T-cell receptor induces a cytosolic Ca ²⁺ signal that is crucial for T-cell function. The Ca ²⁺ channel TRPM2 (transient receptor potential cation channel subfamily M member 2) has been shown to facilitate influx of extracellular Ca ²⁺ 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 Ca ²⁺ 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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Lory, Nawrocki, Corazza, Schmid, Schumacher, Bedke, Menzel, Koch-Nolte, Guse, Huber and Mittrücker.)