Frontiers in Immunology (Jul 2021)

Revisiting the Antigen-Presenting Function of β Cells in T1D Pathogenesis

  • Yang Li,
  • Fei Sun,
  • Tian-Tian Yue,
  • Fa-Xi Wang,
  • Chun-Liang Yang,
  • Jia-Hui Luo,
  • Shan-Jie Rong,
  • Fei Xiong,
  • Shu Zhang,
  • Cong-Yi Wang

DOI
https://doi.org/10.3389/fimmu.2021.690783
Journal volume & issue
Vol. 12

Abstract

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Type 1 diabetes (T1D) is characterized by the unresolved autoimmune inflammation and islet β cell destruction. The islet resident antigen-presenting cells (APCs) including dendritic cells and macrophages uptake and process the β cell-derived antigens to prime the autoreactive diabetogenic T cells. Upon activation, those autoreactive T cells produce copious amount of IFN-γ, TNF-α and IL-1β to induce β cell stress and death. Autoimmune attack and β cell damage intertwine together to push forward this self-destructive program, leading to T1D onset. However, β cells are far beyond a passive participant during the course of T1D development. Herein in this review, we summarized how β cells are actively involved in the initiation of autoimmune responses in T1D setting. Specifically, β cells produce modified neoantigens under stressed condition, which is coupled with upregulated expression of MHC I/II and co-stimulatory molecules as well as other immune modules, that are essential properties normally exhibited by the professional APCs. At the cellular level, this subset of APC-like β cells dynamically interacts with plasmacytoid dendritic cells (pDCs) and manifests potency to activate autoreactive CD4 and CD8 T cells, by which β cells initiate early autoimmune responses predisposing to T1D development. Overall, the antigen-presenting function of β cells helps to explain the tissue specificity of T1D and highlights the active roles of structural cells played in the pathogenesis of various immune related disorders.

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