Regulation of adaptive immunity by the fractalkine receptor during autoimmune inflammation.
Regulation of adaptive immunity by the fractalkine receptor during autoimmune inflammation.
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DOI：
10.4049/jimmunol.1300040
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发表时间：
2013-08-01
期刊：
影响因子：
--
通讯作者：
Cardona AE
中科院分区：
文献类型：
--
作者：
Garcia JA;Pino PA;Mizutani M;Cardona SM;Charo IF;Ransohoff RM;Forsthuber TG;Cardona AE
Fractalkine是一种锚定在神经元或外周内皮细胞上的趋化因子，可作为粘附分子或可溶性化学引诱物。Fractalkine结合小胶质细胞和循环单核细胞、树突细胞和NK细胞上的CX 3CR 1。本研究的目的是确定CX 3CR 1在实验性自身免疫性脑脊髓炎（EAE）期间髓样细胞向中枢神经系统（CNS）的运输和功能中的作用。我们的研究结果表明，在活动性EAE模型中，Cx 3cr 1-/-小鼠表现出更严重的神经功能缺损。骨髓嵌合体小鼠证实，骨髓中CX 3CR 1缺陷增强EAE的严重性。值得注意的是，CX 3CR 1缺陷与CD 115 + Ly 6C-CD 11 c+树突状细胞在EAE受影响的大脑中的积累增加相关，这与脱髓鞘和神经元损伤的增强相关。此外，在CX 3CR 1缺陷小鼠的小脑和脊髓组织中检测到更高的IFN-γ和IL-17水平。对疾病起始期间外周反应的分析显示，在CX 3R 1缺陷的淋巴组织中产生IFN-γ和IL-17的T细胞的频率更高，以及CX 3CR 1缺陷的DC诱导的T细胞增殖增强。此外，与野生型受体相比，过继转移MOG 35 -55反应性野生型T细胞在CX 3CR 1缺陷型受体中诱导了实质上更严重的EAE。总的来说，这些数据表明，除了其在化学吸引中的作用外，CX 3CR 1是骨髓细胞活化的关键调节因子，有助于建立适应性免疫应答。
Fractalkine, a chemokine anchored to neurons or peripheral endothelial cells, serves as an adhesion molecule or as a soluble chemoattractant. Fractalkine binds CX3CR1 on microglia and circulating monocytes, dendritic cells and NK cells. The aim of this study is to determine the role of CX3CR1 in the trafficking and function of myeloid cells to the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE). Our results show that in models of active EAE Cx3cr1–/– mice exhibited more severe neurological deficiencies. Bone marrow chimeric mice confirmed that CX3CR1-deficiency in bone marrow enhanced EAE severity. Notably, CX3CR1 deficiency was associated with an increased accumulation of CD115+Ly6C–CD11c+ dendritic cells into EAE affected brains which correlated with enhanced demyelination and neuronal damage. Furthermore, higher IFN-γ and IL-17 levels were detected in cerebellar and spinal cord tissues of CX3CR1-deficient mice. Analyses of peripheral responses during disease initiation revealed a higher frequency of IFN-γ and IL-17 producing T cells in lymphoid tissues of CX3R1-deficient as well as enhanced T cell proliferation induced by CX3CR1-deficient DCs. In addition, adoptive transfer of MOG35-55 reactive wild type T cells induced substantially more severe EAE in CX3CR1-deficient recipients when compared to wild type recipients. Collectively, the data demonstrate that besides its role in chemoattraction, CX3CR1 is a key regulator of myeloid cell activation contributing to the establishment of adaptive immune responses.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
4.4
作者：
Lauro, Clotilde;Di Angelantonio, Silvia;Limatola, Cristina
通讯作者：
Limatola, Cristina
影响因子：
15.9
作者：
Haskell, CA;Hancock, WW;Charo, IF
通讯作者：
Charo, IF
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR
DOI：
10.4049/jimmunol.1100421
发表时间：
2012-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Mizutani M;Pino PA;Saederup N;Charo IF;Ransohoff RM;Cardona AE
通讯作者：
Cardona AE