Lott Jeremy M, Sumpter Tina L, Turnquist Hēth R
*Starzl Transplantation Institute, Departments of Surgery, Immunology, and Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
*Starzl Transplantation Institute, Departments of Surgery, Immunology, and Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
J Leukoc Biol. 2015 Jun;97(6):1037-48. doi: 10.1189/jlb.3RI1214-595R. Epub 2015 Mar 23.
IL-33 is a more recently identified member of the IL-1 cytokine family, expressed in the nucleus of epithelial cells and released into the extracellular space following tissue damage. The impact of IL-33 as a regulator of the adaptive immune response has been studied extensively, with an understood role for IL-33 in the effector functions of CD4(+) Th2 cells. IL-33, however, is now being shown to initiate the Th2-polarizing function of DCs, and stimulate the secretion of the type 2-associated cytokines, IL-4, IL-5, and IL-13, from tissue-resident innate-immune cells, especially ILCs and MCs. IL-33 also initiates and perpetuates local inflammatory responses through the recruitment and activation of type 2- and inflammatory-associated effectors, such as eosinophils, basophils, and neutrophils. As such, IL-33 drives and amplifies type 2-dependent immunity, as well as type 2-dependent tissue destruction and inflammation. It is also becoming apparent that IL-33 supports the reparative capacity of macrophage and ILCs, but these functions may also contribute to chronic fibrotic diseases. Herein, we review new developments in the understanding of IL-33 as it functions in Th2 cells and type 2 immunity. This includes a discussion of our evolving understanding of how IL-33 directly and indirectly promotes type 2 immune responses through action on innate cells in immunity and the pathogenesis of atopic and fibrotic diseases.
白细胞介素-33（IL-33）是白细胞介素-1细胞因子家族中最近发现的成员，在上皮细胞的细胞核中表达，并在组织损伤后释放到细胞外空间。IL-33作为适应性免疫反应调节因子的作用已得到广泛研究，其在CD4(+) Th2细胞效应功能中的作用已为人所知。然而，现在发现IL-33可启动树突状细胞（DCs）的Th2极化功能，并刺激组织驻留固有免疫细胞，特别是固有淋巴细胞（ILCs）和肥大细胞（MCs）分泌2型相关细胞因子白细胞介素-4（IL-4）、白细胞介素-5（IL-5）和白细胞介素-13（IL-13）。IL-33还通过募集和激活2型及炎症相关效应细胞，如嗜酸性粒细胞、嗜碱性粒细胞和中性粒细胞，启动并维持局部炎症反应。因此，IL-33驱动并放大2型依赖性免疫以及2型依赖性组织破坏和炎症。越来越明显的是，IL-33支持巨噬细胞和ILCs的修复能力，但这些功能也可能导致慢性纤维化疾病。在此，我们综述了对IL-33在Th2细胞和2型免疫中功能的新认识。这包括讨论我们对IL-33如何通过作用于免疫中的固有细胞以及特应性和纤维化疾病的发病机制直接和间接促进2型免疫反应的不断演变的理解。
