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

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.