Tolerogenic dendritic cells specific for β2-glycoprotein-I Domain-I, attenuate experimental antiphospholipid syndrome

Tolerogenic dendritic cells (tDCs) have the potential to control the outcome of autoimmunity by modulating the immune response. The aim of this study was to uncover the tolerance efficacy attributed to beta-2-glycoprotein-I (beta(2)GPI) tDCs or beta(2)GPI domain-I (D-I) and domain-V (D-V)-tDCs in mice with antiphospholipid syndrome CAPS). tDCs were pulsed with beta(2)GPI or D-I or D-V derivatives. Our results revealed that beta(2)GPI related tDCs phenotype includes CD80(high), CD86(high) CD40(high) MHC class IIhigh. The miRNA profiling encompass miRNA 23b(high), miRNA 142-3p(low) and miRNA 221(low). In addition the beta(2)GPI related tDCs showed reduced secretion of IL-1 beta, IL-12 and IL-23. D-I tDCs treatment was more efficient than beta(2)GPI tDCs in inducing of tolerance in APS mice, manifested by lowered titers of anti- beta(2)GPI antibodies (Abs) and reduced percentage of fetal loss. Tolerance induction was accompanied by poor T cell response to beta(2)GPI, high numbers of CD4 + CD25 + FOXP3 + T-regulatory cells (Treg), reduced levels of IFN gamma, IL-17 and increased expression of IL-10 and TGF beta. Tolerance was successfully transferred by Treg cells from the tolerized mice to beta(2)GPI immunized mice. We conclude that predominantly D-I-tDCs and beta(2)GPI tDCs have the potential to attenuate experimental APS by induction of Treg cells, reduction of anti-beta(2)GPI Abs titers and increased expression of anti-inflammatory cytokines. We suggest that (beta(2)-GPI-D-I-tDCs may offer a novel approach for developing therapy for APS patients. (C) 2014 Elsevier Ltd. All rights reserved.