Anti-inflammatory effects of an inflammatory chemokine: CCL2 inhibits lymphocyte homing by modulation of CCL21-triggered integrin-mediated adhesions
Anti-inflammatory effects of an inflammatory chemokine: CCL2 inhibits lymphocyte homing by modulation of CCL21-triggered integrin-mediated adhesions
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DOI：
10.1182/blood-2007-12-129122
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发表时间：
2008-12-15
期刊：
影响因子：
20.3
通讯作者：
Shachar, Idit
中科院分区：
文献类型：
--
作者：
Flaishon, Liat;Hart, Gili;Shachar, Idit
我们的研究重点是限制特定免疫细胞亚群归巢的途径，从而微调特定淋巴组织和外周组织的免疫反应。在这里，我们报告了CCL2（在微摩尔[pM]水平）使小鼠和人T细胞在体外和体内产生ccr7触发的lfa -1激活和lfa -1介导的内皮细胞ICAM-1粘附增强的能力缺陷。CCL2还能减弱淋巴细胞对淋巴结趋化因子的趋化性。因此，低剂量CCL2抑制淋巴细胞向外周淋巴结的归巢，但不影响淋巴细胞通过脾脏的运输。淋巴细胞向外周淋巴结的归巢受损导致哮喘和佐剂性关节炎的减缓进展。因此，pM水平的循环CCL2可以对外周淋巴结内t细胞的运输和分化发挥全局抑制作用，并可能作为抗炎药在临床上有益。（血液杂志，2008;112:5016-5025）
Our studies focus on the pathways that restrict homing of specific subsets of immune cells, and thereby fine-tune the immune response at specific lymphoid and peripheral tissues. Here, we report that CCL2 (at picomolar [pM] levels) renders both murine and human T cells defective in their ability to develop CCR7-triggered activation of LFA-1-and LFA-1-mediated adhesion strengthening to endothelial ICAM-1 both in vitro and in vivo. CCL2 also attenuated lymphocyte chemotaxis toward lymph node chemokines. Consequently, low-dose CCL2 inhibited lymphocyte homing to peripheral lymph nodes but did not affect lymphocyte trafficking through the spleen. Impaired homing of lymphocytes to peripheral lymph nodes resulted in attenuated progression of both asthma and adjuvant arthritis. Thus, pM levels of circulating CCL2 can exert global suppressive effects on T-cell trafficking and differentiation within peripheral lymph nodes, and may be clinically beneficial as an antiinflammatory agent. (Blood. 2008; 112: 5016-5025)