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Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset

Author

Listed:
  • Gregory J. Golden

    (Perelman School of Medicine
    Perelman School of Medicine)

  • Vincent H. Wu

    (Perelman School of Medicine
    Perelman School of Medicine)

  • Jacob T. Hamilton

    (Perelman School of Medicine
    Perelman School of Medicine)

  • Kevin R. Amses

    (Perelman School of Medicine)

  • Melanie R. Shapiro

    (College of Medicine)

  • Alberto Sada Japp

    (Perelman School of Medicine
    Perelman School of Medicine)

  • Chengyang Liu

    (Perelman School of Medicine
    Perelman School of Medicine)

  • M. Betina Pampena

    (Perelman School of Medicine
    Perelman School of Medicine)

  • Leticia Kuri-Cervantes

    (Perelman School of Medicine
    Perelman School of Medicine)

  • James J. Knox

    (Perelman School of Medicine
    Perelman School of Medicine)

  • Jay S. Gardner

    (Perelman School of Medicine
    Perelman School of Medicine)

  • Mark A. Atkinson

    (College of Medicine
    University of Florida)

  • Todd M. Brusko

    (College of Medicine
    University of Florida
    University of Florida)

  • Eline T. Luning Prak

    (Perelman School of Medicine
    Perelman School of Medicine)

  • Klaus H. Kaestner

    (Perelman School of Medicine)

  • Ali Naji

    (Perelman School of Medicine
    Perelman School of Medicine)

  • Michael R. Betts

    (Perelman School of Medicine
    Perelman School of Medicine)

Abstract

Autoimmune destruction of pancreatic β cells results in type 1 diabetes (T1D), with pancreatic immune infiltrate representing a key feature in this process. However, characterization of the immunological processes occurring in human pancreatic lymphatic tissues is lacking. Here, we conduct a comprehensive study of immune cells from pancreatic, mesenteric, and splenic lymphatic tissues of non-diabetic control (ND), β cell autoantibody-positive non-diabetic (AAb+), and T1D donors using flow cytometry and CITEseq. Compared to ND pancreas-draining lymph nodes (pLN), AAb+ and T1D donor pLNs display decreased CD4+ Treg and increased stem-like CD8+ T cell signatures, while only T1D donor pLNs exhibit naive T cell and NK cell differentiation. Mesenteric LNs have modulations only in CD4+ Tregs and naive cells, while splenocytes lack these perturbations. Further, T cell expression of activation markers and IL7 receptor correlate with T1D genetic risk. These results demonstrate tissue-restricted immune changes occur before and after T1D onset.

Suggested Citation

  • Gregory J. Golden & Vincent H. Wu & Jacob T. Hamilton & Kevin R. Amses & Melanie R. Shapiro & Alberto Sada Japp & Chengyang Liu & M. Betina Pampena & Leticia Kuri-Cervantes & James J. Knox & Jay S. Ga, 2025. "Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59626-0
    DOI: 10.1038/s41467-025-59626-0
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