Autoantibody-positivity in lean type II diabetes patients was associated with elevated Th17-like CD4+CXCR5+ T cell responses.

Molecular immunology (2019-06-24)
Yiran Wang, Wenwen Li, Jingjing Zhou, Renhui Wan, Wei Hao, Ye Gao, Yifei He, Rong Chen, Xiao Zhai, Qijin Wang

The pathophysiology of type II diabetes (T2D) in patients with normal body-mass index (BMI) remains unclear. In this study, we investigated the circulating CD4+CXCR5+ T cells in lean T2D patients. Compared with age-, gender-, and BMI-matched healthy controls, the lean T2D patients presented similar frequency and number of CD4+CXCR5+ T cells; however, the composition of CD4+CXCR5+ T subsets was altered. The CD4+CXCR5+ T cells in lean T2D patients were enriched with a Th17-like subset, characterized by an increase in the frequency of IL-17-secreting cells, and an increase in the frequency of CCR6+ cells. Compared to CCR6- CD4+CXCR5+ T cells, CCR6+ CD4+CXCR5+ T cells secreted significantly higher IL-17. Neither the frequency of IL-17-secreting CD4+CXCR5+ T cells, nor the frequency of CCR6+ CD4+CXCR5+ T cells, was associated with the BMI of the T2D patients. Interestingly, 10 out of 30 lean T2D patients in our cohort presented islet-reactive autoantibodies. Compared to the autoantibody-negative T2D patients, the autoantibody-positive T2D patients had significantly higher levels of IL-17-secreting CD4+CXCR5+ T cells and CCR6+ CD4+CXCR5+ T cells. In addition, compared to the CCR6- CD4+CXCR5+ T cells, the CCR6+ CD4+CXCR5+ T cells were more effective at promoting Ig secretion from autologous B cells. Together, this study demonstrated that an upregulation of Th17-like CD4+CXCR5+ T cells was present in lean T2D patients and was associated with autoantibody positivity.