C-reactive protein directly suppresses T helper 1 cell differentiation and alleviates experimental autoimmune encephalomyelitis

Human C-reactive protein (CRP) is a serum soluble pattern recognition receptor (PRR) that serves as a marker of inflammation and directly contributes to innate immunity. Herein we show that human CRP also directly contributes to adaptive immunity, i.e. native CRP binds specifically to human Jurkat T cells and to mouse naïve CD4 + T cells and modulates their T helper (Th) 1 and Th2 responses. In vitro both exogenously added (purified) and endogenously expressed (via transfection) human CRP inhibited Th1 differentiation and augmented Th2 differentiation of naïve CD4 + T cells. In vivo for human CRP transgenic (CRPtg) compared to wild type mice, a lesser proportion of the T cells recovered from the spleens of healthy animals were Th1 cells. Moreover in both CRPtg mice and in wild type mice treated with human CRP, during myelin oligodendrocyte glycoprotein peptide induced experimental autoimmune encephalomyelitis both the Th1 cell response and disease severity were inhibited. These pattern recognition-independent actions of CRP directly on T cells highlights the potential for this soluble PRR to act as a tonic regulator of immunity, shaping global adaptive immune responses during both homeostasis and disease.