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Myeloid cells, key players in atherosclerosis, take up and present antigens, leading to systemic and local T cell activation. The recruitment and activation of immune cells to the aorta in atherosclerosis is regulated by adhesion molecules, chemokines and cytokines. IL-27R is an immunoregulatory signaling nod in autoimmune and infectious pathologies. IL-27R was shown to suppress T cells activation in atherosclerosis, however it’s possible role in myeloid cell accumulation and activation is not understood. Here we demonstrate that Apoe^−/−Il27ra^−/− mice fed with “Western Diet” for 7 or 18 weeks developed significantly more atherosclerosis compared to Apoe^−/−Il27ra^+/− controls. Accelerated disease was driven by enhanced expression of adhesion molecules and chemokines causing the accumulation of immune cells. Myeloid cells produced more inflammatory cytokines and upregulated MHCII. Multiphoton …