Clark R B, Bishop-Bailey D, Estrada-Hernandez T, Hla T, Puddington L, Padula S J
Division of Rheumatic Diseases, Department of Medicine, University of Connecticut Medical School, Farmington, CT 06032, USA.
J Immunol. 2000 Feb 1;164(3):1364-71. doi: 10.4049/jimmunol.164.3.1364.
The peroxisome proliferator-activated receptors (PPARs) are a family of transcription factors belonging to the nuclear receptor superfamily. Until recently, the genes regulated by PPARs were those believed to be predominantly associated with lipid metabolism. Recently, an immunomodulatory role for PPAR gamma has been described in cells critical to the innate immune system, the monocyte/macrophage. In addition, evidence for an antiinflammatory role of the PPAR gamma ligand, 15-deoxy-Delta 12,14-PGJ2 (15d-PGJ2) has been found. In the present studies, we demonstrate, for the first time, that murine helper T cell clones and freshly isolated splenocytes express PPAR gamma 1. The PPAR gamma expressed is of functional significance in that two ligands for PPAR gamma, 15d-PGJ2 and a thiazolidinedione, ciglitazone, mediate significant inhibition of proliferative responses of both the T cell clones and the freshly isolated splenocytes. This inhibition is mediated directly at the level of the T cell and not at the level of the macrophage/APC. Finally, we demonstrate that the two ligands for PPAR gamma mediate inhibition of IL-2 secretion by the T cell clones while not inhibiting IL-2-induced proliferation of such clones. The demonstration of the expression and function of PPAR gamma in T cells reveals a new level of immunoregulatory control for PPARs and significantly increases the role and importance of PPAR gamma in immunoregulation.
过氧化物酶体增殖物激活受体（PPARs）是属于核受体超家族的转录因子家族。直到最近，人们认为受PPARs调控的基因主要与脂质代谢相关。最近，已在对先天性免疫系统至关重要的细胞即单核细胞/巨噬细胞中描述了PPARγ的免疫调节作用。此外，还发现了PPARγ配体15-脱氧-Δ12,14-前列腺素J2（15d-PGJ2）具有抗炎作用的证据。在本研究中，我们首次证明小鼠辅助性T细胞克隆和新鲜分离的脾细胞表达PPARγ1。所表达的PPARγ具有功能意义，因为PPARγ的两种配体15d-PGJ2和噻唑烷二酮类药物环格列酮可显著抑制T细胞克隆和新鲜分离的脾细胞的增殖反应。这种抑制作用直接在T细胞水平介导，而不是在巨噬细胞/抗原呈递细胞（APC）水平介导。最后，我们证明PPARγ的两种配体介导T细胞克隆对白细胞介素-2（IL-2）分泌的抑制作用，同时不抑制IL-2诱导的此类克隆的增殖。T细胞中PPARγ的表达和功能的证明揭示了PPARs免疫调节控制的一个新层面，并显著增加了PPARγ在免疫调节中的作用和重要性。
