Internalization of circulating apoptotic cells by splenic marginal zone dendritic cells: dependence on complement receptors and effect on cytokine production
Internalization of circulating apoptotic cells by splenic marginal zone dendritic cells: dependence on complement receptors and effect on cytokine production
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DOI：
10.1182/blood-2002-06-1769
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发表时间：
2003-01-15
期刊：
影响因子：
20.3
通讯作者：
Thomson, AW
中科院分区：
文献类型：
--
作者：
Morelli, AE;Larregina, AT;Thomson, AW
在稳态条件下，由外周组织中的树突状细胞（DC）内化凋亡细胞中包含的自身抗原，随后DC迁移并将自身肽呈递给次级淋巴器官中的T细胞是诱导和维持外周T细胞耐受的关键步骤。我们在这里表明，除了这种交通的凋亡细胞介导的外周组织驻留的DC，脾边缘区DC迅速摄取循环凋亡的白细胞，过程中凋亡细胞衍生的肽到主要组织相容性复合物II类（MHC-II）分子，并获得CD 8 α在其动员脾滤泡的T细胞区域。由于凋亡细胞激活补体，一些补体因子是吞噬作用的调理素，并在维持外周耐受中发挥作用，我们研究了补体受体（CR）在DC吞噬凋亡细胞中的作用。边缘区DC的凋亡细胞摄取部分通过CR 3（CD 11b/CD 18）介导，在较小程度上通过CR 4（CD 11 c/CD 18）介导，并且在低补体血症动物体内显著降低。在吞噬凋亡细胞后，DC表现出促炎细胞因子白细胞介素1 α（IL-1 α）、IL-1 β、IL-6、IL-12 p70和肿瘤坏死因子α（TNF-α）的mRNA水平和分泌水平降低，而对抗炎介质转化生长因子β 1（TGF-β 1）无影响。这种选择性抑制作用至少部分通过C3 bi-CD 11b/CD 18相互作用介导。凋亡细胞/DC相互作用及其结果的表征提供了对凋亡细胞影响DC功能而不破坏外周耐受的机制的深入了解。(C)2003年，美国血液学会。
Under steady-state conditions, internalization of self-antigens embodied in apoptotic cells by dendritic cells (DCs) resident in peripheral tissue followed by DC migration and presentation of self-peptides to T cells in secondary lymphoid organs are key steps for induction and maintenance of peripheral T-cell tolerance. We show here that, besides this traffic of apoptotic cells mediated by peripheral tissue-resident DCs, splenic marginal zone DCs rapidly ingest circulating apoptotic leukocytes, process apoptotic cell-derived peptides into major histocompatibility complex class II (MHC-II) molecules, and acquire CD8alpha during their mobilization to T-cell areas of splenic follicles. Because apoptotic cells activate complement and some complement factors are opsonins for phagocytosis and play roles in the maintenance of peripheral tolerance, we investigated the role of complement receptors (CRs) in relation to phagocytosis of apoptotic cells by DCs. Apoptotic cell uptake by marginal zone DCs was mediated in part via CR3 (CD11b/CD18) and, to a lesser extent, CR4 (CD11c/CD18) and was reduced significantly in vivo in hypo-complementemic animals. Following phagocytosis of apoptotic cells, DCs exhibited decreased levels of mRNA and secretion of the proinflammatory cytokines interleukin 1alpha (IL-1alpha), IL-1beta, IL-6, IL-12p70, and tumor necrosis factor alpha (TNF-alpha), without effect on the anti-inflammatory mediator transforming growth factor beta1 (TGF-beta1). This selective inhibitory effect was at least partially mediated through C3bi-CD11b/CD18 interaction. Characterization of apoptotic cell/DC interaction and its outcome provides insight into the mechanisms by which apoptotic cells affect DC function without disrupting peripheral tolerance. (C) 2003 by The American Society of Hematology.