Department of Comparative Biology and Safety Sciences, Amgen, South San Francisco, California 94080.
Department of Biomarker Development, Genentech, South San Francisco, California 94080.
Cold Spring Harb Perspect Biol. 2019 Feb 1;11(2):a028548. doi: 10.1101/cshperspect.a028548.
Members of the interleukin (IL)-10 family of cytokines play important roles in regulating immune responses during host defense but also in autoimmune disorders, inflammatory diseases, and cancer. Although IL-10 itself primarily acts on leukocytes and has potent immunosuppressive functions, other family members preferentially target nonimmune compartments, such as tissue epithelial cells, where they elicit innate defense mechanisms to control viral, bacterial, and fungal infections, protect tissue integrity, and promote tissue repair and regeneration. As cytokines are prime drug targets, IL-10 family cytokines provide great opportunities for the treatment of autoimmune diseases, tissue damage, and cancer. Yet no therapy in this space has been approved to date. Here, we summarize the diverse biology of the IL-10 family as it relates to human disease and review past and current strategies and challenges to target IL-10 family cytokines for clinical use.
白细胞介素 (IL)-10 家族细胞因子在宿主防御过程中调节免疫反应方面发挥着重要作用,但也与自身免疫性疾病、炎症性疾病和癌症有关。虽然白细胞介素-10(IL-10)本身主要作用于白细胞,具有强大的免疫抑制功能,但其他家族成员则优先靶向非免疫区室,如组织上皮细胞,在这些部位它们引发先天防御机制来控制病毒、细菌和真菌感染,保护组织完整性,并促进组织修复和再生。由于细胞因子是主要的药物靶点,因此白细胞介素-10 家族细胞因子为治疗自身免疫性疾病、组织损伤和癌症提供了巨大的机会。然而,迄今为止,该领域尚无任何疗法获得批准。在这里,我们总结了白细胞介素-10 家族的多样性生物学与人类疾病的关系,并回顾了过去和当前针对白细胞介素-10 家族细胞因子用于临床应用的策略和挑战。