Nfatc2, also known as Nuclear factor of activated T cells 2, is a transcription factor. It is crucial for the effector function of CD8+ T cells, regulating their responses to cancer and infections. It also participates in various biological processes and is involved in multiple signaling pathways. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, are valuable for studying Nfatc2 [1].

In CD8+ T cells, Dapl1 controls Nfatc2 activation. Dapl1 deficiency promotes the expansion of tumour-infiltrating effector memory-like CD8+ T cells and prevents their functional exhaustion, as Nfatc2 activation is required for preventing the functional exhaustion of these cells. Exhausted CD8+ T cells show attenuated Nfatc2 activation due to Tim3-mediated feedback inhibition, and Dapl1 deletion can rescue Nfatc2 activation, preventing the dysfunction of exhausted CD8+ T cells in chronic infection and cancer [1]. In addition, genetic inhibition of Nfatc2 in mice protects against L-asparaginase (ASNase) hypersensitivity. NFATC2-deficient mice immunized with ASNase have lower antigen-specific and total immunoglobulin E (IgE) levels, develop more CD4+ regulatory T cells, and have decreased IgE-mediated mast cell activation compared to wild-type mice [2].

In conclusion, Nfatc2 is essential for the effector function of CD8+ T cells and is involved in regulating immune responses. The study of Nfatc2 using KO/CKO mouse models has revealed its role in CD8+ T cell exhaustion in chronic infection and cancer, as well as in ASNase hypersensitivity, providing insights into potential therapeutic strategies for these disease areas.