Review Article

Autoimmune diseases: targets, biology, and drug discovery

Shu-jie Li1,2, Yan-li Wu1, Juan-hua Chen1, Shi-yi Shen1,3, Jia Duan1,3,4, H. Eric Xu1,5
1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
2 Department of Traditional Chinese Medicine, Fujian Medical University Union Hospital, Fuzhou 350000, China
3 University of Chinese Academy of Sciences, Beijing 100049, China
4 Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China
5 School of Life Science and Technology, Shanghai Tech University, Shanghai 201210, China
Correspondence to: Shu-jie Li:, Jia Duan:, H. Eric Xu:,
DOI: 10.1038/s41401-023-01207-2
Received: 22 March 2023
Accepted: 20 November 2023
Advance online: 14 December 2023


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.
Keywords: autoimmune disease; autoantigen; immunotherapy; type 1 diabetes; insulin; drug discovery

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