Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Centre for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
Curr Allergy Asthma Rep. 2021 Oct 25;21(11):45. doi: 10.1007/s11882-021-01022-x.
The incidence of allergic diseases such as asthma, rhinitis and atopic dermatitis has risen at an alarming rate over the last century. Thus, there is a clear need to understand the critical factors that drive such pathologic immune responses. Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a nuclear receptor that has emerged as an important regulator of multiple cell types involved in the inflammatory response to allergens; from airway epithelial cells to T Helper (TH) cells.
Initial studies suggested that agonists of PPAR-γ could be employed to temper allergic inflammation, suppressing pro-inflammatory gene expression programs in epithelial cells. Several lines of work now suggest that PPAR-γ plays an essential in promoting 'type 2' immune responses that are typically associated with allergic disease. PPAR-γ has been found to promote the functions of TH2 cells, type 2 innate lymphoid cells, M2 macrophages and dendritic cells, regulating lipid metabolism and directly inducing effector gene expression. Moreover, preclinical models of allergy in gene-targeted mice have increasingly implicated PPAR-γ in driving allergic inflammation. Herein, we highlight the contrasting roles of PPAR-γ in allergic inflammation and hypothesize that the availability of environmental ligands for PPAR-γ may be at the heart of the rise in allergic diseases worldwide.
综述目的:在过去的一个世纪里,哮喘、鼻炎和特应性皮炎等过敏性疾病的发病率以惊人的速度上升。因此,人们显然需要了解导致这种病理性免疫反应的关键因素。过氧化物酶体增殖物激活受体-γ(PPAR-γ)是一种核受体,它已成为参与过敏原引起的炎症反应的多种细胞类型的重要调节剂,包括气道上皮细胞和辅助性 T 细胞(TH)。
最新发现:最初的研究表明,PPAR-γ 的激动剂可用于抑制上皮细胞中促炎基因表达程序,从而调节过敏性炎症。现在有几条研究线索表明,PPAR-γ 在促进与过敏性疾病相关的“2 型”免疫反应中起着至关重要的作用。已经发现 PPAR-γ 促进 TH2 细胞、2 型先天淋巴细胞、M2 巨噬细胞和树突状细胞的功能,调节脂质代谢并直接诱导效应基因表达。此外,靶向基因敲除小鼠的过敏症临床前模型越来越表明 PPAR-γ 在驱动过敏炎症中发挥作用。在此,我们强调了 PPAR-γ 在过敏炎症中的相反作用,并假设环境中 PPAR-γ 配体的可用性可能是全球过敏性疾病上升的核心所在。