Vitamin D exerts endogenous control over TH2 cell fate and immune plasticity

Circulating Vitamin D (Vit-D) has emerged as a potent immune modulator in asthma, yet its direct impact on T_H2 cell regulation, the central effectors of allergic inflammation, remains unclear. Preliminary transcriptomic analysis of neonatal cord blood revealed that gestational Vit-D deficiency corresponds to elevated adaptive and innate immune responses, driven by T_H2 immunity and antimicrobial responses related to asthma inflammation. To elucidate cell-specific molecular mechanisms of Vit-D, we differentiated murine T_H2 cells <i>in vitro</i> under conditions mimicking Vit-D sufficiency and deficiency. Our findings demonstrate that Vit-D exposure promotes intracellular calcium ion homeostasis while suppressing prominent inflammatory cytokines characteristic of asthma. Conversely, Vit-D deficiency reprograms T_H2 cell lineage commitment, inducing overexpression of cytolytic molecules and major histocompatibility complex (MHC) class I molecules-traits typically associated with cytotoxicity rather than the canonical helper function. Our findings underscore Vit-D's role in stabilizing T_H2 cell function and fate, offering insights into asthma and autoimmune disorders.