HIRANO Toshio ≪Developmental Immunology≫ “IL-6-STAT3 controls intracellular MHC class II αβ-dimer level through Cathepsin S activity in dendritic cells.”
Publish Immunity, 23: 491-502, 2005.
We previously demonstrated that IL-6 signaling negatively regulates MHC class II (MHCII) levels in dendritic cells (DCs). Here we showed the molecular mechanism behind the IL-6 effect. The IL-6-STAT3 signaling reduced intracellular MHCII αβ dimer, Ii, and h3-DM levels by decreasing an endogenous inhibitor of cathepsins, cystatin C. Importantly, cathepsin S inhibitors or overexpression of cystatin C reversed the effect of IL-6. Conversely, cathepsin S overexpression mimicked the IL-6 effect, which led to suppress LPS-induced surface expression of MHCII in DC and CD4+ T cell activation. IL-6-STAT3 signaling in vivo also decreased cystatin C expression and MHCII αβ dimer levels in DCs. Thus, IL-6-STAT3 signals in DCs regulates MHCII antigen presentation machinery and suppresses CD4(+) T cell-mediated immune responses.