Secretory IgA Induces Tolerogenic Dendritic Cells through SIGNR1 Dampening Autoimmunity in Mice
| Autor: | Aurelie Gestin, Ivan C. Moura, Celine Vaugier, Emilie Tissandie, Renato C. Monteiro, Agnès Lehuen, Hakim Hocini, Julien Diana, Blaise Corthésy, Lucie Beaudoin |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Immunology
Mannose Autoimmunity Bone Marrow Cells Receptors Cell Surface chemical and pharmacologic phenomena Biology Inhibitory postsynaptic potential medicine.disease_cause Mice 03 medical and health sciences chemistry.chemical_compound fluids and secretions 0302 clinical medicine Immune system stomatognathic system Immune Tolerance medicine Animals Humans Immunology and Allergy Lectins C-Type Receptor 030304 developmental biology 0303 health sciences Type 1 diabetes Multiple sclerosis Cell Differentiation Dendritic Cells Flow Cytometry medicine.disease 3. Good health Mice Inbred C57BL chemistry Gene Knockdown Techniques Immunoglobulin A Secretory Cell Adhesion Molecules Function (biology) 030215 immunology |
| Zdroj: | Journal of Immunology |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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 Ca2+ 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. |
| Databáze: | OpenAIRE |
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