Emerging evidence shows that metabolic regulation may be a critical mechanism in B cell activation and function. As targets of several most widely used immunosuppressants, Ca²⁺ signaling and calcineurin may play an important role in regulating B cell metabolism. Here, we demonstrate that IP₃R-mediated Ca²⁺ signaling and calcineurin regulate B cell proliferation and survival by activating metabolic reprogramming in response to B cell receptor (BCR) stimulation. Both IP₃R-triple-knockout (IP₃R-TKO) and calcineurin inhibition dramatically suppress the metabolic switch in oxidative phosphorylation and glycolysis of stimulated B cells through regulation of glucose uptake, glycolytic enzyme expression, and mitochondrial remodeling, leading to impaired cell-cycle entry and survival. In addition, IP₃R-Ca²⁺ acts as a master regulator of the calcineurin-MEF2C-Myc pathway in driving B cell metabolic adaptations. As genetic defects of IP₃Rs were recently identified as a new class of inborn errors of immunity, these results have important implications for understanding the pathogenesis of such diseases.

Cardiovascular diseases are increasingly recognized as immune-inflammatory disorders in which adaptive immunity shapes tissue injury, repair, and long-term remodeling. T cells are central to these processes because they integrate antigen recognition, lineage-defining transcriptional programs, tissue trafficking, cytokine production, and immunological memory. In this Review, we synthesize current evidence on the Krüppel-like factor (KLF) family as a transcriptional framework linking T-cell biology to cardiovascular disease. KLF2 primarily regulates T-cell quiescence and trafficking, KLF10 supports regulatory T-cell suppressive function and immune-metabolic fitness, KLF4 contributes to inflammatory effector differentiation, and KLF13 regulates delayed inflammatory chemokine expression and, in thymocyte models, exerts a survival-restraining effect through apoptosis-related pathways. Across atherosclerosis, myocardial infarction, myocarditis, hypertension, and heart failure, these KLF-dependent programs may influence the balance between pathogenic effector responses and protective regulatory mechanisms. The strongest direct disease-specific evidence currently supports a role for KLF10 within the CD4⁺ T-cell lineage in experimental atherosclerosis, with complementary functional evidence implicating Treg–macrophage interactions, whereas the roles of KLF-dependent T-cell programs in other cardiovascular settings remain mechanistically compelling but less fully validated. Future progress will require disease-specific T-cell-restricted models, spatially resolved immune analyses, and cell-selective translational strategies to define the therapeutic relevance of the KLF–T-cell axis.