p150/95 (CD11c/CD18) expression is required for the development of experimental autoimmune encephalomyelitis
p150/95 (CD11c/CD18) expression is required for the development of experimental autoimmune encephalomyelitis
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DOI：
10.2353/ajpath.2007.061016
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发表时间：
2007-06-01
影响因子：
6
通讯作者：
Barnum, Scott R.
中科院分区：
文献类型：
--
作者：
Bullard, Daniel C.;Hu, Xianzhen;Barnum, Scott R.
P150/95(CD11c/CD18，CR4)是黏附分子O-2-整合素家族的成员，被认为是一种重要的吞噬细胞受体。P150/95在包括多发性硬化症在内的中枢神经系统脱髓鞘疾病的发生发展中的作用尚不清楚。为了探讨P150/95在实验性自身免疫性脑脊髓炎(EAE)中的作用机制，我们利用CD11c缺陷(CD11c(-/-))小鼠进行了EAE。CD11c(-/-)小鼠的EAE显著减弱，其特征是脊髓T细胞的浸润和这些细胞产生的干扰素-γ显著减少。过继地将抗原再刺激的T细胞从野生型小鼠转移到CD11c(-/-)小鼠可显著减弱EAE，而将CD11c(-/-)抗原再刺激的T细胞转移到对照组小鼠则引起非常轻微的单相EAE。来自MOG(35-55)肽免疫的CD11c(-/-)小鼠的T细胞表现出一种不寻常的细胞因子表型，与对照组相比，IL-2、IL-4和IL-12水平升高，而干扰素-γ、肿瘤坏死因子-α、IL-10、IL-17和转化生长因子-P水平降低。总体而言，在MOG(35-55)重新刺激下，来自预刺激的小鼠的CD11c(-/-)T细胞的增殖与对照T细胞的增殖相似。我们的结果表明，P150/95在T细胞和其他白细胞上的表达对脱髓鞘疾病的发展至关重要，并可能成为多发性硬化症的一个新的治疗靶点。
p150/95 (CD11c/CD18, CR4) is a member of the O-2-integrin family of adhesion molecules and is considered an important phagocytic receptor. The role of p150/95 in the development of central nervous system demyelinating diseases, including multiple sclerosis, remains unexplored. To determine p150/95mediated mechanisms in experimental autoimmune encephalomyelitis (EAE), we performed EAE using CD11c-deficient (CD11c(-/-)) mice. EAE in CD11c(-/-) mice was significantly attenuated and characterized by markedly reduced spinal cord T-cell infiltration and interferon-gamma production by these cells. Adoptive transfer of antigen-restimulated T cells from wildtype to CD11c(-/-) mice produced significantly attenuated EAE, whereas transfer of CD11c(-/-) antigen-restimulated T cells to control mice induced a very mild, monophasic EAE. T cells from MOG(35-55) peptide-primed CD11c(-/-) mice displayed an unusual cytokine phenotype with elevated levels of interleukin (IL)-2, IL-4, and IL-12 but reduced levels of interferon-gamma, tumor necrosis factor-alpha, IL-10, IL-17, and transforming growth factor-P compared with control mice. Overall, CD11c(-/-) T cells from primed mice proliferated comparably to that of control T cells on MOG(35-55) restimulation. Our results indicate that expression of p150/95 is critical on both T cells as well as other leukocytes for the development of demyelinating disease and may represent a novel therapeutic target for multiple sclerosis.