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

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.

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