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Publication : NFAT1 and NFAT2 Differentially Regulate CTL Differentiation Upon Acute Viral Infection.

First Author  Xu T Year  2019
Journal  Front Immunol Volume  10
Pages  184 PubMed ID  30828328
Mgi Jnum  J:294340 Mgi Id  MGI:6445282
Doi  10.3389/fimmu.2019.00184 Citation  Xu T, et al. (2019) NFAT1 and NFAT2 Differentially Regulate CTL Differentiation Upon Acute Viral Infection. Front Immunol 10:184
abstractText  CD8(+) T cell differentiation orchestrated by transcription regulators is critical for balancing pathogen eradication and long-term immunity by effector and memory CTLs, respectively. The transcription factor Nuclear Factor of Activated T cells (NFAT) family members are known for their roles in T cell development and activation but still largely undetermined in CD8(+) T cell differentiation in vivo. Here, we interrogated the role of two NFAT family members, NFAT1 and NFAT2, in the effector and memory phase of CD8(+) T cell differentiation using LCMV(Arm) acute infection model. We found that NFAT1 is critical for effector population generation whereas NFAT2 is required for promoting memory CTLs in a cell intrinsic manner. Moreover, we found that mice lacking both NFAT1 and NFAT2 in T cells display a significant increase in KLRG1(hi) CD127(hi) population and are unable to clear an acute viral infection. NFAT-deficient CTLs showed different degrees of impaired IFN-gamma and TNF-alpha expression with NFAT1 being mainly responsible for IFN-gamma production upon ex-vivo stimulation as well as for antigen-specific cytotoxicity. Our results suggest that NFAT1 and NFAT2 have distinct roles in mediating CD8(+) T cell differentiation and function.
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