Fig. 1.

Cystatin C regulates immunity at cellular and molecular levels.

Under pathological conditions, various stimuli cause variations in Cst C levels. Decreased Cst C up-regulates the activities of cathepsins, facilitating the cell matrix degradation, and IgG1 and IL-10 production to ensure a Th2-like response in favor of parasite proliferation. In addition, decreased Cst C promotes the interference of cathepsin with MHC-II loading in APCs to suppress host immunity against pathogen invasion. Increased or exogenously added Cst C in IFN-γ induced macrophages, on the other hand, down-regulates the cathepsin activities to increase IL-12, TNF-α, and NO generation that shift the immune responses towards protective Th1 immunity. Alternatively, Cst C can also disturb immmune homeostasis independent of cathepsins by antagonizing the binding of TGF-β to its receptor, or directly causing inflammation through formation of Cst C fibrils deposited in vascular walls.

Cystatin C, Cst C; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor kappa light chain enhancer of activated B cells; ROS, reactive oxygen species; IgG2, immunoglobulin G 2; TNF-α, tumor necrosis factor-α; NO, nitric oxide; IFN-γ, interferon-γ; TGF-β, transforming growth factor β.