Regulation of ultraviolet radiation induced cutaneous photoimmunosuppression by toll-like receptor-4.
Regulation of ultraviolet radiation induced cutaneous photoimmunosuppression by toll-like receptor-4.
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DOI：
10.1016/j.abb.2011.01.005
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发表时间：
2011-04-15
影响因子：
3.9
通讯作者：
Yusuf N
中科院分区：
文献类型：
--
作者：
Lewis W;Simanyi E;Li H;Thompson CA;Nasti TH;Jaleel T;Xu H;Yusuf N
UVB辐射是一种有效的免疫抑制剂，可抑制细胞介导的免疫反应。UVB辐射影响细胞介导的免疫反应的机制一直是广泛研究的主题。然而，先天免疫在光免疫过程中的作用却很少受到关注。本研究的目的是确定Toll样受体-4（TLR 4）是否有助于UV诱导的接触性超敏反应（CHS）的抑制。对TLR 4-/-和野生型C57 BL/6（TLR 4 +/+）小鼠进行局部UVB免疫抑制方案，包括100 mJ/cm 2 UVB辐射，然后用半抗原DNFB致敏。野生型TLR 4 +/+小鼠表现出显著的接触性超敏反应抑制，而TLR 4 −/−小鼠表现出显著较少的抑制。野生型TLR 4 +/+小鼠中的抑制可以过继转移到幼稚的同基因受体。此外，在UV照射的TLR 4 −/−小鼠的引流淋巴结中，表达Foxp 3的CD 4 + CD 25+调节性T细胞显著少于TLR 4 +/+小鼠。当在UVB暴露后比较这两种品系中的细胞因子水平时，来自TLR 4 +/+小鼠的T细胞产生较高水平的IL-10和TGF-β以及较低水平的IFN-γ和IL-17。抑制TLR 4的策略可能使我们能够开发用于管理UVB诱导的皮肤免疫抑制的免疫预防和免疫抑制方法。
UVB radiation is a potent immunosuppressive agent that inhibits cell-mediated immune responses. The mechanisms by which UVB radiation influences cell-mediated immune responses have been the subject of extensive investigation. However, the role of innate immunity on photoimmunological processes has received little attention. The purpose of this study was to determine whether toll-like receptor-4 (TLR4) contributed to UV-induced suppression of contact hypersensitivity (CHS) responses. TLR4−/− and wild type C57BL/6 (TLR4+/+) mice were subjected to a local UVB immunosuppression regimen consisting of 100 mJ/cm2 UVB radiation followed by sensitization with the hapten DNFB. Wild type TLR4+/+ mice exhibited significant suppression of contact hypersensitivity response, whereas TLR4−/− developed significantly less suppression. The suppression in wild type TLR4+/+ mice could be adoptively transferred to naïve syngeneic recipients. Moreover, there were significantly fewer Foxp3 expressing CD4+CD25+ regulatory T-cells in the draining lymph nodes of UV-irradiated TLR4−/− mice than TLR4+/+ mice. When cytokine levels were compared in these two strains after UVB exposure, T-cells from TLR4+/+ mice produced higher levels of IL-10 and TGF-β and lower levels of IFN-γ and IL-17. Strategies to inhibit TLR4 may allow us to develop immunopreventive and immunotherapeutic approaches for management of UVB induced cutaneous immunosuppression.