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Autoimmune diseases: targets, biology, and drug discovery

Acta Pharmacologica Sinica volume 45, pages 674–685 (2024)Cite this article

Abstract

Autoimmune diseases (AIDs) arise from a breakdown in immunological self-tolerance, wherein the adaptive immune system mistakenly attacks healthy cells, tissues and organs. AIDs impose excessive treatment costs and currently rely on non-specific and universal immunosuppression, which only offer symptomatic relief without addressing the underlying causes. AIDs are driven by autoantigens, targeting the autoantigens holds great promise in transforming the treatment of these diseases. To achieve this goal, a comprehensive understanding of the pathogenic mechanisms underlying different AIDs and the identification of specific autoantigens are critical. In this review, we categorize AIDs based on their underlying causes and compile information on autoantigens implicated in each disease, providing a roadmap for the development of novel immunotherapy regimens. We will focus on type 1 diabetes (T1D), which is an autoimmune disease characterized by irreversible destruction of insulin-producing β cells in the Langerhans islets of the pancreas. We will discuss insulin as possible autoantigen of T1D and its role in T1D pathogenesis. Finally, we will review current treatments of TID and propose a potentially effective immunotherapy targeting autoantigens.

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Fig. 1: The pathogenesis of autoimmune disease.
Fig. 2: Hypothesis of autoantigen-based therapy for autoimmune diseases.
Fig. 3: Risk factors and disease progression stage of T1D.
Fig. 4: Mechanism of β cell death mediated by T cells in T1D.
Fig. 5: Treatment strategies for type T1D.

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Acknowledgements

This work was supported by CAS Strategic Priority Research Program (XDB37030103 to HEX); Shanghai Municipal Science and Technology Major Project (2019SHZDZX02 to HEX); Shanghai Municipal Science and Technology Major Project (HEX); The National Natural Science Foundation of China (32130022, 82121005); the Lingang Laboratory Grant (LG-GG-202204-01 to HEX); the National Key R&D Program of China (2018YFA0507002 to HEX). Figures were drawn by using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/)

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Authors and Affiliations

  1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China

    Shu-jie Li, Yan-li Wu, Juan-hua Chen, Shi-yi Shen, Jia Duan & H. Eric Xu

  2. Department of Traditional Chinese Medicine, Fujian Medical University Union Hospital, Fuzhou, 350000, China

    Shu-jie Li

  3. University of Chinese Academy of Sciences, Beijing, 100049, China

    Shi-yi Shen & Jia Duan

  4. Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, 528400, China

    Jia Duan

  5. School of Life Science and Technology, Shanghai Tech University, Shanghai, 201210, China

    H. Eric Xu

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  1. Shu-jie Li
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Li, Sj., Wu, Yl., Chen, Jh. et al. Autoimmune diseases: targets, biology, and drug discovery. Acta Pharmacol Sin 45, 674–685 (2024). https://doi.org/10.1038/s41401-023-01207-2

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