Immobilized immune complexes effectively promote the recruitment of FcyRIII (CD16)- expressing human blood dendritic cells

Abstract

Fcy receptor (FCyR)-mediated interaction of soluble and tissue bond immune complexes (ICs) with dendritic cells (DCs) contributes to IC-triggered antimicrobial and autoimmune inflammatory responses. Among human blood CD1c- CD11c + DCs we previously identified the distinct subset of 6-sulfo LacNAc(slan)DCs, characterized by a pronounced expression of FcyRIII (CD16) and potent proinflammatory capacities. We show that CD16 expression equips slanDCs with an exceptional capacity to capture small soluble ICs. Moreover, by applying a flow chamber assay and time-lapse video microscopy, we show that surface-immobilized ICs alone are highly effective in mediating the firm arrest of slanDCs under physiological shear stress conditions. Contrarily, neither immobilized chemokine (ie. CX3CL1) nor complement (i.e. C5a) promote shear-resistant adhesion of slanDC, despite marked expression of the respective surface receptors. Notably, ICs fail to mediate adhesion of other human DC subsets (i.e. plasmocytoid DC and CD1c + DC) or isolated T cells. By blocking selective FcyRs on slanDCs, we demonstrate that their shear-resistant adhesion to immobilized ICs critically depends on CD16, while CD32 (FcyRII) expression is entirely dispensable. Additional studies confirmed enhanced CD16/IC-mediated arrest of slanDCs on monolayers of human dermal microvascular endothelial cells that were pre-incubated with anti-endothelial cell IgG antibodies. Collectively, we identified CD16 as a critical structure for 1) the capture of soluble ICs and 2) the effective, shear-resistant adhesion of circulating proinflammatory slanDCs to immobilized ICs at the endothelial interface. Our data provide first evidence for a novel conduit of rapid FcR-coordinated recruitment of DC in IC-mediated tissue inflammation. JSID AbstractsJournal of Dermatological ScienceVol. 69Issue 2Preview Full-Text PDF