Chemokine-like receptor-1 expression by central nervous system-infiltrating leukocytes and involvement in a model of autoimmune demyelinating disease.
Chemokine-like receptor-1 expression by central nervous system-infiltrating leukocytes and involvement in a model of autoimmune demyelinating disease.
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DOI：
10.4049/jimmunol.0803435
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发表时间：
2009-11-15
期刊：
影响因子：
--
通讯作者：
Butcher EC
中科院分区：
文献类型：
--
作者：
Graham KL;Zabel BA;Loghavi S;Zuniga LA;Ho PP;Sobel RA;Butcher EC
我们研究了趋化因子样受体1（CMKLR 1）在实验性自身免疫性脑脊髓炎（EAE）中的参与，EAE是人类多发性硬化症的模型。在用髓鞘少突胶质细胞糖蛋白氨基酸35-55（MOG 35 -55）主动免疫诱导EAE后，如通过流式细胞术分析所确定的，小胶质细胞和CNS浸润的髓样树突状细胞表达CMKLR 1。此外，CMKLR 1的天然配体chemerin在EAE小鼠的CNS中上调。我们发现，CMKLR 1缺陷（CMKLR 1敲除（KO））小鼠比野生型（WT）小鼠发生更严重的临床和组织学疾病。CMKLR 1 KO淋巴细胞在体外增殖并产生促炎细胞因子，但MOG 35 -55反应性CMKLR 1 KO淋巴细胞通过过继转移至WT或CMKLR 1 KO受体诱导EAE的能力不足。此外，CMKLR 1 KO受体不能完全支持转移的MOG反应性WT淋巴细胞诱导EAE。这些结果暗示CMKLR 1参与疾病的诱导和效应阶段。我们的结论是CMKLR 1参与了EAE的炎症机制，并代表了多发性硬化症的潜在治疗靶点。
We examined the involvement of chemokine-like receptor-1 (CMKLR1) in experimental autoimmune encephalomyelitis (EAE), a model of human multiple sclerosis. Upon EAE induction by active immunization with myelin oligodendrocyte glycoprotein amino acids 35–55 (MOG35–55), microglial cells and CNS-infiltrating myeloid dendritic cells expressed CMKLR1, as determined by flow cytometric analysis. In addition, chemerin, a natural ligand for CMKLR1, was up-regulated in the CNS of mice with EAE. We found that CMKLR1-deficient (CMKLR1 knockout (KO)) mice develop less severe clinical and histologic disease than their wild-type (WT) counterparts. CMKLR1 KO lymphocytes proliferate and produce proinflammatory cytokines in vitro, yet MOG35–55-reactive CMKLR1 KO lymphocytes are deficient in their ability to induce EAE by adoptive transfer to WT or CMKLR1 KO recipients. Moreover, CMKLR1 KO recipients fail to fully support EAE induction by transferred MOG-reactive WT lymphocytes. The results imply involvement of CMKLR1 in both the induction and effector phases of disease. We conclude that CMKLR1 participates in the inflammatory mechanisms of EAE and represents a potential therapeutic target in multiple sclerosis.
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DOI：
10.1097/nen.0b013e31816fc975
发表时间：
2008-05-01
影响因子：
3.2
作者：
Lande, Roberto;Gafa, Valerie;Coccia, Eliana Marina
通讯作者：
Coccia, Eliana Marina
DOI：
10.1084/jem.20080129
发表时间：
2009-01-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Albanesi C;Scarponi C;Pallotta S;Daniele R;Bosisio D;Madonna S;Fortugno P;Gonzalvo-Feo S;Franssen JD;Parmentier M;De Pità O;Girolomoni G;Sozzani S
通讯作者：
Sozzani S
影响因子：
32.4
作者：
Shinohara, Mari L.;Kim, June-Ho;Garcia, Virgilio A.;Cantor, Harvey
通讯作者：
Cantor, Harvey
DOI：
10.1073/pnas.0710487105
发表时间：
2008-01-08
影响因子：
11.1
作者：
Barnea, Gilad;Strapps, Walter;Lee, Kevin J.
通讯作者：
Lee, Kevin J.
影响因子：
82.9
作者：
Greter, M;Heppner, FL;Becher, B
通讯作者：
Becher, B