Revisiting CCL22 in autoimmune diseases: pathogenesis and clinical implications

CCL22 (macrophage-derived chemokine, MDC) is an important member of the CC chemokine family. By binding to its receptor CCR4, it regulates immune cell trafficking, plays a dual role in maintaining immune homeostasis and promotes immune-mediated inflammation. The biological effects of CCL22-CCR4 signaling in autoimmune diseases are highly dependent on the tissue microenvironment. Under steady-state conditions, CCL22 secreted by dendritic cells and macrophages recruits regulatory T-cells (Tregs) to peripheral tissues, suppresses excessive immune responses, and maintains immune tolerance. When CCL22 expression is down-regulated, Treg recruitment becomes insufficient, leading to immune dysregulation and tissue injury. CCL22 plays a critical role in the pathogenesis of several autoimmune diseases including vitiligo, systemic lupus erythematosus, and type 1 diabetes, although its biological effects vary across different disease contexts. This review focuses on the central roles of the CCL22-CCR4 axis in immune tolerance and inflammatory responses and describes how its functions are finely regulated by cell type, tissue microenvironment, and signaling states in different disease contexts.