title: Cutting edge: intravenous Ig inhibits invariant NKT cell-mediated allergic airway inflammation through FcγRIIIA-dependent mechanisms.
abstract: Despite their increasing use in autoimmune, inflammatory, and allergic conditions, the mechanism of action of i.v. Igs (IVIg) is poorly understood. On the basis of the critical role of invariant NKT (iNKT) cells in allergic airway inflammation (AAI) and their constitutive expression of the low-affinity IgG receptor FcγRIIIA, we surmised that IVIg targets iNKT cells to exert their anti-inflammatory effect. We found that IVIg treatment significantly inhibited AAI in OVA-sensitized C57BL/6 mice and downregulated α-galactosylceramide-induced iNKT cell activation and cytokine production. Allergic responses were restored in iNKT cell-deficient mice by transferring iNKT cells from PBS- but not from IVIg-treated mice, suggesting that IVIg acts directly on activated iNKT cells that have a critical role in AAI. The inhibitory effects of IVIg on both iNKT cell activation/function and OVA-driven AAI were lost in FcγRIIIA(-/-) mice. Our data unravel an FcγRIIIA-dependent inhibitory effect of IVIg on activated iNKT cells that confers protection in AAI.
authors.affiliation: Unité Mixte de Recherche 8147, Centre National de la Recherche Scientifique, Hôpital Necker, Paris 75783, France.
authors.forename: Luiza M
authors.initials: LM
authors.lastname: Araujo
authors.forename: Angélique
authors.initials: A
authors.lastname: Chauvineau
authors.forename: Ren
authors.initials: R
authors.lastname: Zhu
authors.forename: Séverine
authors.initials: S
authors.lastname: Diem
authors.forename: Elvire A
authors.initials: EA
authors.lastname: Bourgeois
authors.forename: Anaïs
authors.initials: A
authors.lastname: Levescot
authors.forename: Michel
authors.initials: M
authors.lastname: Huerre
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Gombert
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
authors.forename: Marc
authors.initials: M
authors.lastname: Daëron
authors.forename: Pierre
authors.initials: P
authors.lastname: Bruhns
authors.forename: Srini V
authors.initials: SV
authors.lastname: Kaveri
authors.forename: André
authors.initials: A
authors.lastname: Herbelin
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000627:therapeutic use; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology / Q000628:therapy; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005699:Galactosylceramides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016756:Immunoglobulins, Intravenous / Q000502:physiology* / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000502:physiology* / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D010047:Ovalbumin / Q000276:immunology / Q000633:toxicity; D017452:Receptors, IgG / Q000502:physiology* / Q000627:therapeutic use; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000637:transplantation
chemical_list: D000485:Allergens; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D005699:Galactosylceramides; D016756:Immunoglobulins, Intravenous; D018836:Inflammation Mediators; D017452:Receptors, IgG; C493154:alpha-galactosylceramide; D010047:Ovalbumin