INSERM U1016, Cochin Institute, Paris 75014, France.
J Immunol. 2013 Sep 1;191(5):2335-43. doi: 10.4049/jimmunol.1300864. Epub 2013 Aug 7.
IgA plays ambivalent roles in the immune system. The balance between inhibitory and activating responses relies on the multimerization status of IgA and interaction with their cognate receptors. In mucosal sites, secretory IgA (SIgA) protects the host through immune-exclusion mechanisms, but its function in the bloodstream remains unknown. Using bone marrow-derived dendritic cells, we found that both human and mouse SIgA induce tolerogenic dendritic cells (DCs) following binding to specific ICAM-3 grabbing nonintegrin receptor 1. This interaction was dependent on Ca(2+) and mannose residues. SIgA-primed DCs (SIgA-DCs) are resistant to TLR-dependent maturation. Although SIgA-DCs fail to induce efficient proliferation and Th1 differentiation of naive responder T cells, they generate the expansion of regulatory T cells through IL-10 production. SIgA-DCs are highly potent in inhibiting autoimmune responses in mouse models of type 1 diabetes and multiple sclerosis. This discovery may offer new insights about mucosal-derived DC immunoregulation through SIgA opening new therapeutic approaches to autoimmune diseases.
IgA 在免疫系统中发挥着双重作用。抑制和激活反应之间的平衡依赖于 IgA 的多聚化状态及其与同源受体的相互作用。在黏膜部位，分泌型 IgA（SIgA）通过免疫排斥机制保护宿主，但它在血液中的功能尚不清楚。使用骨髓来源的树突状细胞，我们发现人源和鼠源 SIgA 在与特定的 ICAM-3 抓取非整合素受体 1 结合后，均可诱导耐受性树突状细胞（DC）。这种相互作用依赖于 Ca(2+)和甘露糖残基。SIgA 致敏的 DC（SIgA-DC）对 TLR 依赖性成熟具有抗性。虽然 SIgA-DC 不能诱导初始应答 T 细胞的有效增殖和 Th1 分化，但它们通过产生 IL-10 来扩增调节性 T 细胞。SIgA-DC 在抑制 1 型糖尿病和多发性硬化症的小鼠模型中的自身免疫反应方面非常有效。这一发现可能为黏膜来源的 DC 免疫调节提供新的见解，为自身免疫性疾病开辟新的治疗方法。
