STIM1-mediated NFAT signaling synergizes with STAT1 to control T-bet expression and T_H1 differentiation.

ABSTRACT: Stromal interaction molecule 1 (STIM1) is critical for store-operated Ca²⁺ entry (SOCE) and T cell activation. T helper 1 (T_H1) cells, which express T-bet (encoded by TBX21), mediate immunity to intracellular pathogens. Although SOCE is known to regulate other T_H lineages, its role in Th1 differentiation remains unclear. Here, we report a patient with an intronic loss-of-function mutation in STIM1, which abolishes SOCE and causes immunodeficiency. We demonstrate that SOCE promotes nuclear factor of activated T cells (NFAT) binding to conserved noncoding sequence (CNS)-12 in the TBX21 enhancer and enables NFAT to synergize with STAT1 to mediate TBX21 expression. While SOCE-deficient CD4⁺ T cells have reduced expression of TBX21 in the absence of i

SUBMITTER: Zhong L 

PROVIDER: S-EPMC12121662 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature