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TGF-β-mediated crosstalk between TIGIT+ Tregs and CD226+CD8+ T cells in the progression and remission of type 1 diabetes

Author

Listed:
  • Ting Zhong

    (The Second Xiangya Hospital of Central South University)

  • Xinyu Li

    (The Second Xiangya Hospital of Central South University)

  • Kang Lei

    (The Second Xiangya Hospital of Central South University)

  • Rong Tang

    (The Second Xiangya Hospital of Central South University)

  • Qiaolin Deng

    (Karolinska Institute)

  • Paul E Love

    (National Institutes of Health)

  • Zhiguang Zhou

    (The Second Xiangya Hospital of Central South University)

  • Bin Zhao

    (The Second Xiangya Hospital of Central South University
    Central South University
    Furong Laboratory)

  • Xia Li

    (The Second Xiangya Hospital of Central South University)

Abstract

Type 1 diabetes (T1D) is a chronic autoimmune condition characterized by hyperglycemia resulting from the destruction of insulin-producing β-cells that is traditionally deemed irreversible, but partial remission (PR) with temporary reversal of hyperglycemia is sometimes observed. Here we use single-cell RNA sequencing to delineate the immune cell landscape across patients in different T1D stages. Together with cohort validation and functional assays, we observe dynamic changes in TIGIT+CCR7− Tregs and CD226+CCR7−CD8+ cytotoxic T cells during the peri-remission phase. Machine learning algorithms further identify TIGIT+CCR7− Tregs and CD226+CD8+ T cells as biomarkers for β-cell function decline in a predictive model, while cell communication analysis and in vitro assays suggest that TIGIT+CCR7− Tregs may inhibit CD226+CCR7−CD8+ T cells via TGF-β signaling. Lastly, in both cyclophosphamide-induced and streptozotocin (STZ)-induced mouse diabetes models, CD226 inhibition postpones insulitis onset and reduces hyperglycemia severity. Our results thus identify two interrelated immune cell subsets that may serve as biomarkers for monitoring disease progression and targets for therapeutic intervention of T1D.

Suggested Citation

  • Ting Zhong & Xinyu Li & Kang Lei & Rong Tang & Qiaolin Deng & Paul E Love & Zhiguang Zhou & Bin Zhao & Xia Li, 2024. "TGF-β-mediated crosstalk between TIGIT+ Tregs and CD226+CD8+ T cells in the progression and remission of type 1 diabetes," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53264-8
    DOI: 10.1038/s41467-024-53264-8
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