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Article

Allergen-Induced C5a/C5aR1 Axis Activation in Pulmonary CD11b+ cDCs Promotes Pulmonary Tolerance through Downregulation of CD40

1
Institute for Systemic Inflammation Research, University of Lübeck, 23562 Lübeck, Germany
2
Cell Analysis Core, University of Lübeck, 23562 Lübeck, Germany
3
Airway Research Center North, Member of the German Center for Lung Research (DZL), 23562 Lübeck, Germany
4
Division of Immunobiology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
*
Author to whom correspondence should be addressed.
Cells 2020, 9(2), 300; https://doi.org/10.3390/cells9020300
Received: 20 December 2019 / Revised: 20 January 2020 / Accepted: 23 January 2020 / Published: 26 January 2020
(This article belongs to the Special Issue The Molecular and Cellular Basis for Allergies & Asthma)
Activation of the C5/C5a/C5a receptor 1 (C5aR1) axis during allergen sensitization protects from maladaptive T cell activation. To explore the underlying regulatory mechanisms, we analyzed the impact of C5aR1 activation on pulmonary CD11b+ conventional dendritic cells (cDCs) in the context of house-dust-mite (HDM) exposure. BALB/c mice were intratracheally immunized with an HDM/ovalbumin (OVA) mixture. After 24 h, we detected two CD11b+ cDC populations that could be distinguished on the basis of C5aR1 expression. C5aR1 but not C5aR1+ cDCs strongly induced T cell proliferation of OVA-reactive transgenic CD4+ T cells after re-exposure to antigen in vitro. C5aR1 cDCs expressed higher levels of MHC-II and CD40 than their C5aR1+ counterparts, which correlated directly with a higher frequency of interactions with cognate CD4+ T cells. Priming of OVA-specific T cells by C5aR1+ cDCs could be markedly increased by in vitro blockade of C5aR1 and this was associated with increased CD40 expression. Simultaneous blockade of C5aR1 and CD40L on C5aR1+ cDCs decreased T cell proliferation. Finally, pulsing with OVA-induced C5 production and its cleavage into C5a by both populations of CD11b+ cDCs. Thus, we propose a model in which allergen-induced autocrine C5a generation and subsequent C5aR1 activation in pulmonary CD11b+ cDCs promotes tolerance towards aeroallergens through downregulation of CD40. View Full-Text
Keywords: allergic asthma; complement; conventional dendritic cell; C5a receptor; CD40; house-dust-mite allergic asthma; complement; conventional dendritic cell; C5a receptor; CD40; house-dust-mite
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MDPI and ACS Style

Antoniou, K.; Ender, F.; Vollbrandt, T.; Laumonnier, Y.; Rathmann, F.; Pasare, C.; Singh, H.; Köhl, J. Allergen-Induced C5a/C5aR1 Axis Activation in Pulmonary CD11b+ cDCs Promotes Pulmonary Tolerance through Downregulation of CD40. Cells 2020, 9, 300. https://doi.org/10.3390/cells9020300

AMA Style

Antoniou K, Ender F, Vollbrandt T, Laumonnier Y, Rathmann F, Pasare C, Singh H, Köhl J. Allergen-Induced C5a/C5aR1 Axis Activation in Pulmonary CD11b+ cDCs Promotes Pulmonary Tolerance through Downregulation of CD40. Cells. 2020; 9(2):300. https://doi.org/10.3390/cells9020300

Chicago/Turabian Style

Antoniou, Konstantina, Fanny Ender, Tillman Vollbrandt, Yves Laumonnier, Franziska Rathmann, Chandrashekhar Pasare, Harinder Singh, and Jörg Köhl. 2020. "Allergen-Induced C5a/C5aR1 Axis Activation in Pulmonary CD11b+ cDCs Promotes Pulmonary Tolerance through Downregulation of CD40" Cells 9, no. 2: 300. https://doi.org/10.3390/cells9020300

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