Szatmari Istvan, Rajnavolgyi Eva, Nagy Laszlo
Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, H-4010, Hungary.
Ann N Y Acad Sci. 2006 Nov;1088:207-18. doi: 10.1196/annals.1366.013.
In recent years it became apparent that PPARgamma, besides being a key component of adipose tissue development and a target of insulin-sensitizing drugs, also has a role in immune cell differentiation and function. This receptor has been identified by us and others as a conductor of lipid handling in macrophages, and has roles also in inflammation control. Here we review recent advances on the role of this nuclear receptor in another key cell type of myeloid origin, dendritic cells (DCs). DCs are professional antigen-presenting cells having essential roles in antigen-uptake processing and presentation and in initiation of various forms of immune responses. It appears that PPARgamma is expressed and is active in myeloid DCs and likely to be a regulator of DC function by altering antigen uptake, maturation, activation, migration, cytokine production, and lipid antigen presentation. Thus PPARgamma is at the crossroads of lipid metabolism and innate immune response, and by studying its functions one has a unique opportunity to discern how these two seemingly distant fields (lipid metabolism and immune response) are interrelated. It is also possible that this receptor is a relevant target for pharmacological intervention in immune diseases such as chronic inflammation and autoimmune conditions.
近年来,很明显,过氧化物酶体增殖物激活受体γ(PPARγ)除了是脂肪组织发育的关键组成部分和胰岛素增敏药物的靶点外,在免疫细胞分化和功能方面也发挥作用。我们和其他人已将该受体鉴定为巨噬细胞中脂质处理的指挥者,并且在炎症控制中也发挥作用。在此,我们综述了这种核受体在另一种关键的髓系起源细胞类型——树突状细胞(DCs)中的作用的最新进展。DCs是专职抗原呈递细胞,在抗原摄取、加工和呈递以及启动各种形式的免疫反应中起重要作用。似乎PPARγ在髓系DCs中表达且具有活性,并且可能通过改变抗原摄取、成熟、激活、迁移、细胞因子产生和脂质抗原呈递来调节DC功能。因此,PPARγ处于脂质代谢和固有免疫反应的交叉点,通过研究其功能,人们有独特的机会了解这两个看似遥远的领域(脂质代谢和免疫反应)是如何相互关联的。这种受体也有可能是慢性炎症和自身免疫性疾病等免疫疾病中药物干预的相关靶点。