A selective role for the TNF p55 receptor in autocrine signaling following IFN-γ stimulation in experimental autoimmune uveoretinitis
A selective role for the TNF p55 receptor in autocrine signaling following IFN-γ stimulation in experimental autoimmune uveoretinitis
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DOI：
10.4049/jimmunol.175.10.6286
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发表时间：
2005-11-15
影响因子：
4.4
通讯作者：
Dick, AD
中科院分区：
文献类型：
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作者：
Calder, CJ;Nicholson, LB;Dick, AD
IFN-γ刺激巨噬细胞活化和NO产生，这导致实验性自身免疫性葡萄膜视网膜炎中视网膜的破坏。在这项研究中，我们研究了TNF p55受体缺陷动物的抗病机制。我们表明，虽然T细胞的启动是相对不受影响的，缺乏TNF p55受体的巨噬细胞不能产生一氧化氮IFN-γ刺激后，因为需要通过TNF p55受体自分泌TNF-α信号。与受损的NO合成激活相反，在用IFN-γ刺激的野生型和TNFRp 55（-/-）小鼠中，MHC II类上调是不可区分的。这些缺陷可以通过用LPS刺激巨噬细胞来克服。总之，这些结果表明，IFN-γ活化的选定方面是由TNF-γ的自分泌分泌控制的，但这种控制在病原体相关分子模式识别受体产生的信号存在下丧失。
IFN-gamma stimulates macrophage activation and NO production, which leads to destruction of the retina in experimental autoimmune uveoretinitis. In this study, we investigate the mechanism of disease resistance in TNF p55 receptor-deficient animals. We show that although T cell priming is relatively unaffected, macrophages lacking the TNF p55 receptor fail to produce NO following IFN-gamma stimulation because of a requirement for autocrine TNF-alpha signaling through the TNF p55 receptor. In contrast to the impaired activation of NO synthesis, MHC class II up-regulation was indistinguishable in wild-type and TNFRp55(-/-) mice stimulated with IFN-gamma. These defects could be overcome by stimulating macrophages with LPS. Together, these results show that selected aspects of IFN-gamma activation are controlled by autocrine secretion of TNF-gamma, but that this control is lost in the presence of signals generated by pathogen-associated molecular patterns recognizing receptors.