Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland; Division of Dermatology and Venereology, University Hospitals of Geneva, Geneva, Switzerland.
J Allergy Clin Immunol. 2021 Jul;148(1):40-52. doi: 10.1016/j.jaci.2020.12.628. Epub 2021 Jan 20.
IL-25, also known as IL-17E, is a unique cytokine of the IL-17 family. Indeed, IL-25 exclusively was shown to strongly induce expression of the cytokines associated with type 2 immunity. Although produced by several types of immune cells, such as T cells, dendritic cells, or group 2 innate lymphoid cells, a vast amount of IL-25 derives from epithelial cells. The functions of IL-25 have been actively studied in the context of physiology and pathology of various organs including skin, airways and lungs, gastrointestinal tract, and thymus. Accumulating evidence suggests that IL-25 is a "barrier surface" cytokine whose expression depends on extrinsic environmental factors and when upregulated may lead to inflammatory disorders such as atopic dermatitis, psoriasis, or asthma. This review summarizes the progress of the recent years regarding the effects of IL-25 on the regulation of immune response and the balance between its homeostatic and pathogenic role in various epithelia. We revisit IL-25's general and tissue-specific mechanisms of action, mediated signaling pathways, and transcription factors activated in immune and resident cells. Finally, we discuss perspectives of the IL-25-based therapies for inflammatory disorders and compare them with the mainstream ones that target IL-17A.
白细胞介素 25（IL-25），又名白细胞介素 17E（IL-17E），是白细胞介素 17 家族中的一种独特细胞因子。事实上，IL-25 被证明能强烈诱导与 2 型免疫相关的细胞因子表达。尽管它可由多种免疫细胞产生，如 T 细胞、树突状细胞或 2 型先天淋巴细胞，但大量的 IL-25 源自上皮细胞。IL-25 的功能已在包括皮肤、气道和肺部、胃肠道和胸腺在内的各种器官的生理和病理生理学中得到了积极研究。越来越多的证据表明，IL-25 是一种“屏障表面”细胞因子，其表达取决于外在环境因素，而上调时可能导致特应性皮炎、银屑病或哮喘等炎症性疾病。本文综述了近年来关于 IL-25 对免疫反应调节的影响及其在各种上皮组织中稳态和致病作用之间平衡的研究进展。我们重新探讨了 IL-25 的一般和组织特异性作用机制、介导的信号通路以及在免疫细胞和固有细胞中被激活的转录因子。最后，我们讨论了基于 IL-25 的疗法治疗炎症性疾病的前景，并将其与靶向白细胞介素 17A 的主流疗法进行了比较。
