Leukocyte attraction through the CCR5 receptor controls progress from insulitis to diabetes in nonobese diabetic mice
Leukocyte attraction through the CCR5 receptor controls progress from insulitis to diabetes in nonobese diabetic mice
复制标题
DOI：
10.1002/eji.200324285
复制
发表时间：
2004-02-01
影响因子：
5.4
通讯作者：
Martinez, C
中科院分区：
文献类型：
--
作者：
Carvalho-Pinto, C;García, MI;Martinez, C
淋巴细胞浸润到胰岛与化学吸引有关，其他炎症性自身免疫过程也是如此。我们研究了胰岛炎和糖尿病的发展是否依赖于通过CCR5趋化因子受体对淋巴细胞的化学吸引。在非肥胖糖尿病（NOD）小鼠中，大量外周T细胞和几乎所有B细胞表达高水平的CCR 5。CCR5的表达特征的效应T细胞表型，表明它们在疾病的发展中的潜在参与。鉴于这些发现和CCL5（RANTES，CCR5配体）在胰岛中的表达，我们用中和性抗CCR5抗体治疗NOD小鼠。这并不影响胰岛周围炎的进展，但抑制了β细胞破坏和糖尿病。这些数据表明CCR5依赖性化学吸引在胰岛炎进展至胰岛破坏中的作用，表明通过CCR5靶向进行治疗性干预的潜在价值。
Lymphocyte infiltration to pancreatic islets is associated to chemoattraction, as are other inflammatory autoimmune processes. We examined whether development of insulitis and diabetes depends on chemoattraction of lymphocytes via the CCR5 chemokine receptor. In non-obese diabetic (NOD) mice, a substantial fraction of peripheral T cells and virtually all B cells expressed high CCR5 levels. CCR5 expression characterized the effector T cell phenotype, suggesting their potential involvement in disease development. In view of these findings and the CCL5 (RANTES, the CCR5 ligand) expression by pancreatic islets, we treated NOD mice with a neutralizing anti-CCR5 antibody. This did not influence peri-insulitis advancement, but inhibited beta-cell destruction and diabetes. These data demonstrate a role of CCR5-dependent chemoattraction in insulitis progression to islet destruction, suggesting the potential value of therapeutic intervention by CCR5 targeting.