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The Roles of Interleukin-18 in Inflammation and Autoimmune Disease
Yue Zhao1, Yuan Tang1,2, Xiaoxia Zhu3
1Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, China.
None:
Interleukin-18 (IL-18) is a member of the IL-1 cytokine family with significant homology to IL-1β. New emerging evidence indicates that IL-18 acts as a pivotal molecular bridge connecting innate and adaptive immunity, functioning through tightly regulated mechanisms involving inflammasome-dependent and -independent proteolytic processing. The activity of IL-18 is primarily maintained by IL-18 binding protein (IL-18BP), which neutralizes IL-18 under physiological conditions. However, dysregulations in the IL-18/IL-18BP axis result in excessive IL-18 bioactivity, driving tissue inflammation and damage closely associated with autoimmune pathogenesis. Herein, we review recent advances in IL-18 biology and its expanding roles in the development of various autoimmune diseases. The molecular mechanisms by which IL-18 mediates organ-specific pathology are discussed to highlight its diverse effector functions across different autoimmune conditions. In addition, we evaluate emerging therapeutic approaches targeting the IL-18 pathway, with a focus on their potential and challenges in translational clinical research.
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