Skoberne Mojca, Somersan Selin, Almodovar Wanda, Truong Tuan, Petrova Kseniya, Henson Peter M, Bhardwaj Nina
New York University School of Medicine, 550 First Ave, MSB 507, New York, NY 10016, USA.
Blood. 2006 Aug 1;108(3):947-55. doi: 10.1182/blood-2005-12-4812. Epub 2006 Apr 13.
Dendritic cells (DCs) that capture apoptotic cells (ACs) in the steady state mediate peripheral tolerance to self-antigens. ACs are recognized by an array of receptors on DCs, the redundancy of which is not completely defined. We made use of an AC surrogate system to address the individual roles of the alphavbeta5 and complement receptors (CRs) in the phagocytosis and induction of immunity. CR3 and CR4, while substantially less efficient than alphavbeta5 in internalizing ACs, initiate signals that render DCs tolerogenic. Responding T cells show impaired proliferation and IFNgamma production and subsequently die by apoptosis. While tolerogenic DCs are not induced via alphavbeta5, coligation of CR3 and alphavbeta5 maintains the DC's tolerogenic profile. This immunomodulatory role, however, is countered by a significant inflammatory stimulus such as bacterial infection. Overall, our data suggest that under steady-state conditions, signaling via CRs predominates to render DCs tolerogenic.
在稳态下捕获凋亡细胞（AC）的树突状细胞（DC）介导对外源自身抗原的外周耐受。AC可被DC上一系列受体识别，这些受体的冗余性尚未完全明确。我们利用一种AC替代系统来研究αvβ5和补体受体（CR）在吞噬作用和免疫诱导中的各自作用。CR3和CR4虽然在摄取AC方面远不如αvβ5有效，但能启动使DC具有耐受性的信号。反应性T细胞的增殖和IFNγ产生受损，随后通过凋亡死亡。虽然通过αvβ5不会诱导产生耐受性DC，但CR3和αvβ5的共同结合可维持DC的耐受性特征。然而，这种免疫调节作用会被诸如细菌感染等显著的炎症刺激所抵消。总体而言，我们的数据表明，在稳态条件下，通过CR发出的信号占主导地位，使DC具有耐受性。
