Large-scale and diverse analysis of the single-cell transcriptomes of PBMCs from children diagnosed with Type 1 diabetes (T1D)
Our cohort included 22 children with newly diagnosed diabetes, 20 children with established T1D, their immediate relatives (parents (N=4), siblings (N=4)), and conditionally healthy individuals (N=12). For CD4+ effector and regulatory T-cells, we revealed specific cell populations accompanying active autoimmune destruction. We uncovered that the level of Th22 is associated with upregulation of TNF and IL-6, a decrease in MAIT cells accompanied by alteration of their functional activity, and involvement of ADAM10 and ADAM17 in the elevation of proinflammatory intercellular signaling. The completion of the autoimmune process is characterized by an increase in the level of Th17, associated with the effects of TGF-ß1 and IL-12. Moreover, the increase in the naive Tregs fraction characterizes the new-onset stage of T1D, followed by the clinical manifestation of the disease. Investigation of transcriptional regulation via BACH2 revealed its crucial role in the maturation of Treg cells. The level of naive T-regulatory and CD4+ effector cells, accompanied by alterations in cell-cell communication at certain stages of autoimmune destruction in T1D, suggests new biomarkers of disease stages and targets for possible therapy.