Differential regulation of C5a receptor 1 in innate immune cells during the allergic asthma effector phase.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Asthma/*immunology ; Lung/*immunology ; Receptor, Anaphylatoxin C5a/*immunology; Animals ; Asthma/pathology ; CD11b Antigen/analysis ; CD11b Antigen/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/pathology ; Dendritic Cells/immunology ; Dendritic Cells/pathology ; Eosinophils/immunology ; Eosinophils/pathology ; Immunity, Cellular ; Lung/pathology ; Macrophages/immunology ; Macrophages/pathology ; Mediastinum/pathology ; Mice ; Myeloid Cells/immunology ; Myeloid Cells/pathology ; Ovalbumin/immunology ; Receptor, Anaphylatoxin C5a/analysis

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.

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0 (C5ar1 protein, mouse)
0 (CD11b Antigen)
0 (Receptor, Anaphylatoxin C5a)
9006-59-1 (Ovalbumin)

Date Created: 20170224 Date Completed: 20170817 Latest Revision: 20190208

20250114

PMC5322932

10.1371/journal.pone.0172446

28231307