title: The regulatory dendritic cell marker C1q is a potent inhibitor of allergic inflammation.
abstract: The complement subunit C1q was recently identified as a marker for monocyte-derived regulatory dendritic cells supporting the differentiation of interleukin (IL)-10-secreting CD4+T cells with a suppressive activity. Furthermore, C1q expression is upregulated in peripheral blood mononuclear cells of allergic patients in the course of successful allergen immunotherapy. Herein, we investigated a potential direct role of C1q in downregulating allergic inflammation. In mice with ovalbumin (OVA) or birch pollen (BP)-induced allergic asthma, C1q is as efficacious as dexamethasone to reduce both airway hyperresponsiveness (AHR), eosinophil, and ILC2 infiltrates in bronchoalveolar lavages, as well as allergen-specific T helper 2 cells in the lungs. Administration of C1q does not expand IL-10+/Foxp3+regulatory T cells in the lungs, spleen, or in the blood. Depletion of plasmacytoid dendritic cells (pDCs) abrogates the capacity of C1q to reduce AHR and eosinophilic infiltrates in OVA-sensitized mice. Also C1q treatment inhibits the activation of human and mouse pDCs by CpGs, thereby demonstrating a critical role for pDCs in the anti-inflammatory activity of C1q. We conclude that regulatory dendritic cells can mediate a potent direct anti-inflammatory activity via the expression and/or secretion of molecules such as C1q, independently of their capacity to expand the pool of regulatory T cells.
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: L
authors.initials: L
authors.lastname: Mascarell
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: S
authors.initials: S
authors.lastname: Airouche
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: N
authors.initials: N
authors.lastname: Berjont
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.|CEA, Fontenay-aux-roses, France.
authors.forename: C
authors.initials: C
authors.lastname: Gary
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: C
authors.initials: C
authors.lastname: Gueguen
authors.affiliation: CNRS UMR7211 & INSERM U959, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Fourcade
authors.affiliation: CNRS UMR7211 & INSERM U959, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Bellier
authors.affiliation: Artimmune SAS, Orléans, France.
authors.forename: D
authors.initials: D
authors.lastname: Togbe
authors.affiliation: CNRS UMR 7355-University of Orléans, Orléans, France.
authors.forename: B
authors.initials: B
authors.lastname: Ryffel
authors.affiliation: CNRS UMR7211 & INSERM U959, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Klatzmann
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: V
authors.initials: V
authors.lastname: Baron-Bodo
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: P
authors.initials: P
authors.lastname: Moingeon
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D029662:Betula; D002478:Cells, Cultured; D015922:Complement C1q / Q000008:administration & dosage / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D016753:Interleukin-10 / Q000378:metabolism; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010936:Plant Extracts; D011058:Pollen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000485:Allergens; D010936:Plant Extracts; D016753:Interleukin-10; D015922:Complement C1q; D010047:Ovalbumin