Differences in Maturation Status and Immune Phenotypes of Circulating Helios+ and Helios− Tregs and Their Disrupted Correlations With Monocyte Subsets in Autoantibody-Positive T1D Individuals.

Autor: Zhang, Yuyue, Zhang, Jie, Shi, Yun, Shen, Min, Lv, Hui, Chen, Shu, Feng, Yingjie, Chen, Heng, Xu, Xinyu, Yang, Tao, Xu, Kuanfeng
Předmět:
Zdroj: Frontiers in Immunology; 5/12/2021, Vol. 12, pN.PAG-N.PAG, 13p
Abstrakt: CD4 Tregs are involved in the regulation of various autoimmune diseases but believed to be highly heterogeneous. Studies have indicated that Helios controls a distinct subset of functional Tregs. However, the immunological changes in circulating Helios+ and Helios Tregs are not fully explored in type 1 diabetes (T1D). Here, we elucidated the differences in maturation status and immune regulatory phenotypes of Helios+ and Helios Tregs and their correlations with monocyte subsets in T1D individuals. As CD25−/low FOXP3+ Tregs also represent a subset of functional Tregs, we defined Tregs as FOXP3+CD127−/low and examined circulating Helios+ and Helios Treg subpopulations in 68 autoantibody-positive T1D individuals and 68 age-matched healthy controls. We found that expression of both FOXP3 and CTLA4 diminished in Helios Tregs, while the proportion of CD25−/low Tregs increased in Helios+ Tregs of T1D individuals. Although the frequencies of neither Helios+ nor Helios Tregs were affected by investigated T1D genetic risk loci, Helios+ Tregs correlated with age at T1D diagnosis negatively and disease duration positively. Moreover, the negative correlation between central and effector memory proportions of Helios+ Tregs in healthy controls was disrupted in T1D individuals. Finally, regulatory non-classical and intermediate monocytes also decreased in T1D individuals, and positive correlations between these regulatory monocytes and Helios+/Helios Treg subsets in healthy controls disappeared in T1D individuals. In conclusion, we demonstrated the alternations in maturation status and immune phenotypes in Helios+ and Helios Treg subsets and revealed the missing association between these Treg subsets and monocyte subsets in T1D individuals, which might point out another option for elucidating T1D mechanisms. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index