Endogenous Cortisol and TGF-β in Human Aqueous Humor Contribute to Ocular Immune Privilege by Regulating Dendritic Cell Function
Endogenous Cortisol and TGF-β in Human Aqueous Humor Contribute to Ocular Immune Privilege by Regulating Dendritic Cell Function
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DOI：
10.4049/jimmunol.1001450
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发表时间：
2011-01-01
影响因子：
4.4
通讯作者：
Curnow, S. John
中科院分区：
文献类型：
--
作者：
Denniston, Alastair K.;Kottoor, Sherine H.;Curnow, S. John
在动物模型中，房水(AQH)被证明对APC具有显著的免疫抑制作用。我们想要确定，在人类中，AQH是否可以调节树突状细胞(DC)的功能，并确定相关的主导机制。人AQH体外抑制人外周血单核细胞来源的DC诱导幼稚的CD4(+)T细胞增殖和细胞因子产生的能力，与共刺激分子CD86的DC表达减少有关。在非炎症条件下培养的DC(未成熟的DC)和在促炎细胞因子刺激的DC(成熟的DC)中都可以看到这一点。MHC I/II类和CD83类DC表达减少(仅成熟DC)。外周血中的髓样DC对人AQH的影响也同样敏感，但仅在炎症条件下。在生理水平上，α-黑素细胞刺激素和血管活性肠肽的加入没有引起明显的抑制作用。然而，生理水平外源性皮质醇的加入重现了AQH诱导的CD86减少和DC诱导的T细胞增殖抑制，阻断AQH的皮质醇部分逆转了其抑制作用。转化生长因子-β2对皮质醇有额外的作用，尽管同时阻断皮质醇和转化生长因子-β2降低了其作用效果，但仍存在皮质醇和转化生长因子-β非依赖性成分。在人类中，AQH通过皮质醇和转化生长因子-β2的联合作用调节DC的成熟和功能，这一途径可能有助于维持眼睛的免疫豁免权。免疫学杂志，2011,186：305-311。
Aqueous humor (AqH) has been shown to have significant immunosuppressive effects on APCs in animal models. We wanted to establish whether, in humans, AqH can regulate dendritic cell (DC) function and to identify the dominant mechanism involved. Human AqH inhibited the capacity of human peripheral blood monocyte-derived DC to induce naive CD4(+) T cell proliferation and cytokine production in vitro, associated with a reduction in DC expression of the costimulatory molecule CD86. This was seen both for DC cultured under noninflammatory conditions (immature DC) and for DC stimulated by proinflammatory cytokines (mature DC). DC expression of MHC classes I/II and CD83 was reduced (mature DC only). Myeloid DC from peripheral blood were similarly sensitive to the effects of human AqH, but only under inflammatory conditions. The addition of a-melanocyte stimulating hormone and vasoactive intestinal peptide did not cause significant inhibition at physiological levels. However, the addition of exogenous cortisol at physiological levels recapitulated the AqH-induced reduction in CD86 and inhibition of DC-induced T cell proliferation, and blockade of cortisol in AqH partially reversed its suppressive effects. TGF-beta 2 had an additional effect with cortisol, and although simultaneous blockade of cortisol and TGF-beta 2 in AqH reduced its effectiveness, there was still a cortisol-and TGF-beta-independent component. In humans, AqH regulates DC maturation and function by the combined actions of cortisol and TGF-beta 2, a pathway that is likely to contribute to the maintenance of immune privilege in the eye. The Journal of Immunology, 2011, 186: 305-311.