Allergen-Induced C5a/C5aR1 Axis Activation in Pulmonary CD11b+ cDCs Promotes Pulmonary Tolerance through Downregulation of CD40
| العنوان: | Allergen-Induced C5a/C5aR1 Axis Activation in Pulmonary CD11b+ cDCs Promotes Pulmonary Tolerance through Downregulation of CD40 |
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| المؤلفون: | Jörg Köhl, Chandrashekhar Pasare, Harinder Singh, Fanny Ender, Tillman Vollbrandt, Konstantina Antoniou, Franziska Rathmann, Yves Laumonnier |
| المصدر: | Cells, Vol 9, Iss 2, p 300 (2020) Cells Volume 9 Issue 2 |
| بيانات النشر: | MDPI AG, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, T cell, Priming (immunology), 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Antigen, medicine, complement, c5a receptor, conventional dendritic cell, Autocrine signalling, lcsh:QH301-705.5, CD40, biology, Chemistry, cd40, General Medicine, respiratory system, Molecular biology, Ovalbumin, 030104 developmental biology, medicine.anatomical_structure, Integrin alpha M, house-dust-mite, lcsh:Biology (General), biology.protein, allergic asthma, 030215 immunology |
| الوصف: | 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&minus but not C5aR1+ cDCs strongly induced T cell proliferation of OVA-reactive transgenic CD4+ T cells after re-exposure to antigen in vitro. C5aR1&minus 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2073-4409 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::758091a1a749f4fe95377d50df02333a https://www.mdpi.com/2073-4409/9/2/300 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....758091a1a749f4fe95377d50df02333a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20734409 |
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