DOI: 10.2337/db23-203-or ISSN: 0012-1797

203-OR: Features of Human Th-Like Regulatory T Cells in the Pathogenesis of Type 1 Diabetes

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Background: The imbalance between Tregs, Bregs and proinflammatory Th cells plays a vital role in the pathogenesis and development of T1D. Accumulating evidence has revealed that Treg has phenotypic plastic changes into other subsets under pathological conditions. However, whether Tregs convert into other immune cell types in T1D and the potential influencing factors remain unknown. This study aimed to examine the changes of Th-like Tregs in T1D patients and determine whether Th cells and IL-10+ Bregs play roles in Treg polarization.

Methods: A total of 49 T1D patients and 20 healthy controls (HC) were recruited in this study. Flow cytometry was used to measure Treg plasticity (including CD4+Foxp3+IFN-γ+ Th1-like, CD4+Foxp3+IL-4+ Th2-like and CD4+Foxp3+IL-17+ Th17-like Tregs), the proportion of CD27+CD39hi Bregs, and Th cell subsets (including Th1, Th2 and Th17 cells) in the peripheral blood. Cytokines were detected by ELISA.

Results: The frequencies of Th1-like Tregs and Th17-like Tregs in T1D were lower than those in HC, while the proportion of Th17 cells was significantly increased in T1D. The frequency of Bregs was markedly higher in T1D relative to HC, but IL-10 expression of Bregs was reduced. Interestingly, compared with lean and overweight patients, Th1-like Tregs were higher in patients with normal weight, but Treg plasticity was not affected by disease status (age at diagnosis, islet autoantibodies and β-cell function) or T1D risk loci (rs3118470 or rs2104286) in IL2RA. Additionally, positive correlations between Th1-like Tregs and Th17-like Tregs and between Bregs and Th2-like Tregs were observed in T1D. Meanwhile, the frequency of Th1-like Tregs was negatively related to IL-6 and the frequency of Th2-like Tregs was negatively associated with TNF-α.

Conclusion: Our results firstly explored the features of human Th-like Tregs in the pathogenesis in T1D, which might contribute to improve our understanding of the pathogenic mechanisms of T1D.


Y.Qin: None. Y.Li: None. L.Dai: None. Q.Wei: None. M.Huang: None. M.Zhang: None.


National Natural Science Foundation of China (81974103, 82000747)

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