The nuclear receptor PPARγ and immunoregulation:: PPARγ mediates inhibition of helper T cell responses
The nuclear receptor PPARγ and immunoregulation:: PPARγ mediates inhibition of helper T cell responses
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DOI：
10.4049/jimmunol.164.3.1364
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发表时间：
2000-02-01
影响因子：
4.4
通讯作者：
Padula, SJ
中科院分区：
文献类型：
--
作者：
Clark, RB;Bishop-Bailey, D;Padula, SJ
过氧化物酶体增殖物激活受体（peroxisome proliferator-activated receptors，PPARs）是核受体超家族中的一个转录因子家族，目前认为PPARs调控的基因主要是与脂质代谢相关的基因。最近，在先天免疫系统的关键细胞单核细胞/巨噬细胞中描述了PPAR γ的免疫调节作用。此外，PPAR γ配体15-脱氧-δ（12，14）- PGJ（2）（15 d-PGJ（2））。在本研究中，我们首次证实小鼠辅助性T细胞克隆和新鲜分离的脾细胞表达PPAR γ 1。15 d-PGJ（2）和噻唑烷二酮环格列酮介导对T细胞克隆和新鲜分离的脾细胞的增殖反应的显著抑制。这种抑制直接在T细胞水平介导，而不是在巨噬细胞/APC水平介导。最后，我们证明了两个配体的过氧化物酶体增殖物激活受体γ介导的抑制IL-2分泌的T细胞克隆，而不抑制IL-2诱导的增殖，这样的克隆。T细胞中PPAR γ的表达和功能的证明揭示了PPAR的免疫调节控制的新水平，并显着增加了PPAR γ在免疫调节中的作用和重要性。
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)- PGJ(2) (15d-PGJ(2)) 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-PGJ(2), 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.