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

Authors:
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

Front Immunol 2021 14;12:690783. Epub 2021 Jul 14.

The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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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Source
http://dx.doi.org/10.3389/fimmu.2021.690783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318689PMC
November 2021

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