title: Differential regulation of C5a receptor 1 in innate immune cells during the allergic asthma effector phase.
abstract: C5a drives airway constriction and inflammation during the effector phase of allergic asthma, mainly through the activation of C5a receptor 1 (C5aR1). Yet, C5aR1 expression on myeloid and lymphoid cells during the allergic effector phase is ill-defined. Recently, we generated and characterized a floxed green fluorescent protein (GFP)-C5aR1 knock-in mouse. Here, we used this reporter strain to monitor C5aR1 expression in airway, pulmonary and lymph node cells during the effector phase of OVA-driven allergic asthma. C5aR1 reporter and wildtype mice developed a similar allergic phenotype with comparable airway resistance, mucus production, eosinophilic/neutrophilic airway inflammation and Th2/Th17 cytokine production. During the allergic effector phase, C5aR1 expression increased in lung tissue eosinophils but decreased in airway and pulmonary macrophages as well as in pulmonary CD11b+ conventional dendritic cells (cDCs) and monocyte-derived DCs (moDCs). Surprisingly, expression in neutrophils was not affected. Of note, moDCs but not CD11b+ cDCs from mediastinal lymph nodes (mLN) expressed less C5aR1 than DCs residing in the lung after OVA challenge. Finally, neither CD103+ cDCs nor cells of the lymphoid lineage such as Th2 or Th17-differentiated CD4+ T cells, B cells or type 2 innate lymphoid cells (ILC2) expressed C5aR1 under allergic conditions. Our findings demonstrate a complex regulation pattern of C5aR1 in the airways, lung tissue and mLN of mice, suggesting that the C5a/C5aR1 axis controls airway constriction and inflammation through activation of myeloid cells in all three compartments in an experimental model of allergic asthma.
authors.affiliation: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
authors.forename: Fanny
authors.initials: F
authors.lastname: Ender
authors.affiliation: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Wiese
authors.affiliation: Institute for Anatomy, University of Lübeck, Lübeck, Germany.
authors.forename: Inken
authors.initials: I
authors.lastname: Schmudde
authors.affiliation: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Cell Analysis Core, University of Lübeck, Lübeck, Germany.
authors.forename: Tillman
authors.initials: T
authors.lastname: Vollbrandt
authors.affiliation: Institute for Anatomy, University of Lübeck, Lübeck, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: König
authors.affiliation: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
authors.forename: Yves
authors.identifier: http://orcid.org/0000-0001-9603-3269
authors.initials: Y
authors.lastname: Laumonnier
authors.affiliation: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.|Division of Immunobiology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
authors.forename: Jörg
authors.initials: J
authors.lastname: Köhl
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D039481:CD11b Antigen / Q000032:analysis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D007111:Immunity, Cellular; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008482:Mediastinum / Q000473:pathology; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology; D044087:Receptor, Anaphylatoxin C5a / Q000032:analysis / Q000276:immunology*
chemical_list: C000591759:C5ar1 protein, mouse; D039481:CD11b Antigen; D044087:Receptor, Anaphylatoxin C5a; D010047:Ovalbumin