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

Differential regulation of C5a receptor 1 in innate immune cells during the allergic asthma effector phase.
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Ender F, Wiese AV, Schmudde I, Sun J, Vollbrandt T, König P, Laumonnier Y, Köhl J,


Ender F, Wiese AV, Schmudde I, Sun J, Vollbrandt T, König P, Laumonnier Y, Köhl J, (click to view)

Ender F, Wiese AV, Schmudde I, Sun J, Vollbrandt T, König P, Laumonnier Y, Köhl J,

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PloS one 2017 02 2312(2) e0172446 doi 10.1371/journal.pone.0172446
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.

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