TRPM2 Is Not Required for T-Cell Activation and Differentiation
FRONTIERS IN IMMUNOLOGY(2022)
摘要
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.
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关键词
TRPM2,T cells,T-cell activation,TCR signaling,ADPR,calcium signaling
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