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

• Published in: Frontiers in immunology 2021-07, Vol.12, p.690783-690783
• Main Authors: Li, Yang, Sun, Fei, Yue, Tian-Tian, Wang, Fa-Xi, Yang, Chun-Liang, Luo, Jia-Hui, Rong, Shan-Jie, Xiong, Fei, Zhang, Shu, Wang, Cong-Yi
• Format: Article
• Language: English
• Subjects: antigen presentation; autoimmune diabetes; crosstalk; Immunology; innate immunity; β cell
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.690783

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.