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

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.