The role of mTORC2/RICTOR in immune cells and inflammatory diseases

BACKGROUND: mTORC2, defined by its core component RICTOR, is a key regulator of immune cell function and inflammation, yet its roles have long been underappreciated due to lack of specific inhibitors and in vivo tools. OBJECTIVE: This review summarizes the current understanding of mTORC2-specific signaling (via AKT, SGK1, and PKC) in regulating the development, differentiation, and effector functions of diverse immune cells, and discusses its emerging roles in immune cell inflammation and tissue-specific inflammation. METHOD: We synthesized findings from recent studies using conditional knockout mouse models, pharmacological inhibitors, and clinical samples. CONCLUSION: mTORC2 controls Th1/Th2 differentiation, Treg stability, and memory T cell formation; regulates BCR signaling and plasma cell survival; and modulates macrophage M2 polarization, DC maturation, and NK cell function. In tissue inflammation, mTORC2 plays context-dependent roles-exacerbating osteoarthritis and pancreatitis but restraining pro-inflammatory polarization in colorectal cancer. Dual mTORC1/2 inhibitors (e.g., AZD2014) have shown early promise, though challenges remain regarding efficacy, toxicity, and immunomodulatory complexity.