胰岛树突状细胞亚群的专属功能
发布时间:2012-10-08 14:58:38浏览次数:3689次来源:吉林大学白求恩第二医院 上海市第六人民医院 摘自: J Immunol 2012; 188:4921-4930; Prepublished online 16 April 2012
树突细胞在1型糖尿病ß细胞的免疫与耐受中起着重要的作用。目前尚不清楚在胰岛中树突状如何分化并执行负性功能。为了解决这些问题,研究对胰岛树突状细胞的亚群及专属功能进行分类。在免疫稳态以及炎症条件下,胰岛主要有两种组织固有树突状细胞,一种是CD11b(lo/-)CD103(+)CX3CR1(-) (CD103(+) DC),主要分化自依赖fms样络氨酸激酶3的树突状细胞前体。另外一种是CD11b(+)CD103(-)CX3CR1(+) (CD11b(+) DC),其主要分化自单核细胞。尽管CD103(+) DC的吞噬作用有限,但它是主要的迁移性的树突状细胞,在胰腺引流淋巴结模型中可以交叉暴露胰岛的抗原。CD11b(+) DC是主要的亚群,约占总数的60-80%,但是,在胰腺引流淋巴结模型中很少发生迁移。CD11b(+) DC有很强的吞噬能力,但是CD11b(+) DC很少将抗原递呈给T细胞。在T细胞介导的胰腺炎中CD11b(+) DC数量增多,这说明CD11b(+) DC在胰腺炎的发病中起重要作用。以上结果阐明了胰岛树突状细胞在免疫稳态及炎症条件下的分型和功能,提示树突状细胞在胰岛免疫的不同作用。
Functional Specialization of Islet Dendritic Cell Subsets
Dendritic cells (DC) play important roles in both tolerance and immunity to β cells in type 1 diabetes. How and why DC can have diverse and opposing functions in islets remains elusive. To answer these questions, islet DC subsets and their specialized functions were characterized. Under both homeostatic and inflammatory conditions, there were two main tissue-resident DC subsets in islets, defined as CD11b(lo/-)CD103(+)CX3CR1(-) (CD103(+) DC), the majority of which were derived from fms-like tyrosine kinase 3-dependent pre-DC, and CD11b(+)CD103(-)CX3CR1(+) (CD11b(+) DC), the majority of which were derived from monocytes. CD103(+) DC were the major migratory DC and cross-presented islet-derived Ag in the pancreatic draining lymph node, although this DC subset displayed limited phagocytic activity. CD11b(+) DC were numerically the predominant subset (60-80%) but poorly migrated to the draining lymph node. Although CD11b(+) DC had greater phagocytic activity, they poorly presented Ag to T cells. CD11b(+) DC increased in numbers and percentage during T cell-mediated insulitis, suggesting that this subset might be involved in the pathogenesis of diabetes. These data elucidate the phenotype and function of homeostatic and inflammatory islet DC, suggesting differential roles in islet immunity.