Distinct immune features in the partial remission phase of type 1 diabetes identified through Single-Cell RNA Sequencing and Functional Analysis

Type 1 diabetes is a progressive autoimmune disease with unknown etiology. Although the destruction of β-cells is recognized as an irreversible process, many type 1 diabetes patients experience the partial remission stage characterized by spontaneous and transient recovery of β-cell function. However, a comprehensive understanding of immune disturbances in the progression of type 1 diabetes as well as the immunological mechanisms responsible for the partial remission stage remains to be elucidated. Here, we applied single-cell RNA sequencing to delineate the immune underpinnings of peripheral immune cells from new-onset type 1 diabetes patients and type 1 diabetes patients in the partial remission phase. Combined with cohort validation and functional assays, we identified Treg and CD8+ T cell subsets with highly transcriptional heterogeneity and distinctive functional programs that exhibited compositional changes during the partial remission stage of type 1 diabetes and were significantly associated with β-cell function. Further analysis revealed that TIGIT+ CCR7- Tregs expanded during the partial remission stage and suppressed highly cytotoxic CD226+ CCR7- CD8+ T cells through TGF-β signal, which suggests that this mechanism may have contributed to the restoration of immune balance during the partial remission stage. These findings provide a framework for enriching our knowledge about type 1 diabetes progression and remission, and the cell subsets we identified may offer mechanistic clues for therapeutic intervention.