The CD14CD16 monocyte subset is expanded and controls Th1 cell development in Graves' disease.

Three different subsets of circulating human monocytes, CD14CD16 (classical), CD14CD16 (intermediate), and CD14CD16 (non-classical) monocytes, have been recently identified. New evidence suggests that levels of intermediate monocytes or CD16 (intermediate and non-classical) monocytes are increased in autoimmune diseases. However, studies regarding the role of each monocyte subset in the pathogenesis of Graves' disease (GD) are lacking. We aimed to investigate the clinical implications of these subsets and their potential role in GD pathogenesis. CD14CD16 monocytes showed a more activated state in GD patients than other monocyte subpopulations. An increased proportion of circulating CD14CD16 monocytes and a decreased proportion of circulating CD14CD16 monocytes in GD patients were detected, and CD14CD16 monocyte frequencies were positively correlated with GD clinical parameters. Additionally, a follow-up analysis indicated that the CD14CD16 monocyte percentage increased and the CD14CD16 monocyte percentage decreased post-treatment. We found that CD14CD16 GD monocytes promoted the expansion of IFN-γCD4 cells. The Th1-polarizing cytokine IL-12, secreted after direct contact with patient CD14CD16 monocytes and CD4 T cells, was responsible for IFN-γCD4 cell development. Our results suggest that CD14CD16 monocytes are involved in GD pathogenesis and the critical role of CD14CD16 monocytes in the generation of potentially pathogenic Th responses in GD.