IL-1R and MyD88 signalling in CD4 + T cells promote Th17 immunity and atherosclerosis

Abstract

The role of CD4 + T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper sub-sets. In this study, we tested the roles of IL-1R1 and MyD88 signalling in CD4 + T cells in atherosclerosis. Methods and results We transferred apoe -/- myd88\+/\+ or apoe -/- myd88 -/- CD4 + T cells to T-A nd B-cell-deficient rag1 -/- apoe -/- mice fed high fat diet. Mice given apoe -/- myd88 -/- CD4 + T cells exhibited reduced atherosclerosis compared with mice given apoe -/- myd88\+/\+ CD4 + T cells. CD4 + T cells from apoe -/- myd88 -/- produced less IL-17 but similar levels of IFN-c. Treatment of human CD4 + T cells with a MyD88 inhibitor inhibited IL-17 secretion in vitro. Transfer of il1r1 -/- CD4 + T cells recapitulated the phenotype seen by transfer of myd88 -/- CD4 + T cells with reduced lesion development and a reduction in Th17 and IL-17 production compared with wild type CD4 + T cell recipients. Relative collagen content of lesions was reduced in mice receiving il1r1 -/- CD4 + T cells. Conclusion We demonstrate that both IL1R and MyD88 signalling in CD4 + T cells promote Th17 immunity, plaque growth and may regulate plaque collagen levels.