Navigating the Paradox of IL‐22: Friend or Foe in Hepatic Health?

ABSTRACT Interleukin‐22 (IL‐22), a cytokine from the IL‐10 family produced by T cells and innate lymphoid cells, plays a crucial role in immune responses and tissue regeneration. Its association with liver disease has garnered significant attention; however, its exact impact remains controversial. This review aims to enhance the current understanding of the dual role of IL‐22 in liver disease by exploring its protective and pathogenic effects. First, we provide an overview of IL‐22 biology, including its source, receptors, and signaling pathways. Subsequently, we offer a comprehensive overview of the dual function of IL‐22 in non‐neoplastic liver disease, emphasizing its antiapoptotic and regenerative properties. We also discuss the applicability of the conclusions drawn from studies on nonalcoholic fatty liver disease to metabolic dysfunction‐associated steatotic liver disease. Furthermore, we elaborate on the intricate role of IL‐22 in hepatocellular carcinoma, particularly its influence on the tumor microenvironment, proliferation, and immune evasion. In conclusion, IL‐22 is paradoxical in liver disease, acting as a friend and foe. It is imperative to understand this paradox to develop targeted therapies that capitalize on the beneficial effects of IL‐22 while mitigating its detrimental effects.