Haddad El-Bdaoui, Cyr Sonya L, Arima Kazuhiko, McDonald Robert A, Levit Noah A, Nestle Frank O
Sanofi, 450 Water Street, Cambridge, MA, USA.
Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
Dermatol Ther (Heidelb). 2022 Jul;12(7):1501-1533. doi: 10.1007/s13555-022-00737-7. Epub 2022 May 21.
Type 2 immunity evolved to combat helminth infections by orchestrating a combined protective response of innate and adaptive immune cells and promotion of parasitic worm destruction or expulsion, wound repair, and barrier function. Aberrant type 2 immune responses are associated with allergic conditions characterized by chronic tissue inflammation, including atopic dermatitis (AD) and asthma. Signature cytokines of type 2 immunity include interleukin (IL)-4, IL-5, IL-9, IL-13, and IL-31, mainly secreted from immune cells, as well as IL-25, IL-33, and thymic stromal lymphopoietin, mainly secreted from tissue cells, particularly epithelial cells. IL-4 and IL-13 are key players mediating the prototypical type 2 response; IL-4 initiates and promotes differentiation and proliferation of naïve T-helper (Th) cells toward a Th2 cell phenotype, whereas IL-13 has a pleiotropic effect on type 2 inflammation, including, together with IL-4, decreased barrier function. Both cytokines are implicated in B-cell isotype class switching to generate immunoglobulin E, tissue fibrosis, and pruritus. IL-5, a key regulator of eosinophils, is responsible for eosinophil growth, differentiation, survival, and mobilization. In AD, IL-4, IL-13, and IL-31 are associated with sensory nerve sensitization and itch, leading to scratching that further exacerbates inflammation and barrier dysfunction. Various strategies have emerged to suppress type 2 inflammation, including biologics targeting cytokines or their receptors, and Janus kinase inhibitors that block intracellular cytokine signaling pathways. Here we review type 2 inflammation, its role in inflammatory diseases, and current and future therapies targeting type 2 pathways, with a focus on AD. INFOGRAPHIC.
2型免疫反应通过协调先天免疫细胞和适应性免疫细胞的联合保护反应以及促进寄生虫的破坏或排出、伤口修复和屏障功能，进化而来以对抗蠕虫感染。异常的2型免疫反应与以慢性组织炎症为特征的过敏性疾病相关，包括特应性皮炎（AD）和哮喘。2型免疫反应的标志性细胞因子包括主要由免疫细胞分泌的白细胞介素（IL）-4、IL-5、IL-9、IL-13和IL-31，以及主要由组织细胞特别是上皮细胞分泌的IL-25、IL-33和胸腺基质淋巴细胞生成素。IL-4和IL-13是介导典型2型反应的关键因子；IL-4启动并促进初始T辅助（Th）细胞向Th2细胞表型的分化和增殖，而IL-13对2型炎症具有多效性作用，包括与IL-4一起降低屏障功能。这两种细胞因子都与B细胞同种型类别转换以产生免疫球蛋白E、组织纤维化和瘙痒有关。IL-5是嗜酸性粒细胞的关键调节因子，负责嗜酸性粒细胞的生长、分化、存活和动员。在AD中，IL-4、IL-13和IL-31与感觉神经致敏和瘙痒有关，导致搔抓，进一步加剧炎症和屏障功能障碍。已经出现了多种抑制2型炎症的策略，包括靶向细胞因子或其受体的生物制剂，以及阻断细胞内细胞因子信号通路的Janus激酶抑制剂。在这里，我们综述2型炎症、其在炎症性疾病中的作用以及针对2型通路的当前和未来疗法，重点是AD。信息图。
