A Critical Role for the CXCL3/CXCL5/CXCR2 Neutrophilic Chemotactic Axis in the Regulation of Type 2 Responses in a Model of Rhinoviral-Induced Asthma Exacerbation
| Autor: | Paul S. Foster, Thi Hiep Nguyen, Ming Yang, Gerard E. Kaiko, Keilah Garcia-Netto, Jason Girkin, Joerg Mattes, Adam Collison, Nathan W. Bartlett, Chi Liu, Leon A. Sokulsky |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Chemokine CXCL5 Chemokine Rhinovirus Exacerbation Neutrophils Immunology Inflammation Receptors Interleukin-8B Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Immunology and Allergy Lymphocytes Lung CCL11 Asthma Mice Inbred BALB C biology business.industry Innate lymphoid cell respiratory system medicine.disease Immunity Innate respiratory tract diseases Eosinophils Chemotaxis Leukocyte CXCL5 biology.protein Bronchial Hyperreactivity medicine.symptom business CCL24 Chemokines CXC 030215 immunology |
| Zdroj: | The Journal of Immunology. 205:2468-2478 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Rhinovirus (RV) infections in asthmatic patients are often associated with asthma exacerbation, characterized by worsened airways hyperreactivity and increased immune cell infiltration to the airways. The C-X-C chemokines, CXCL3 and CXCL5, regulate neutrophil trafficking to the lung via CXCR2, and their expression in the asthmatic lung is associated with steroid-insensitive type 2 inflammatory signatures. Currently, the role of CXCL3 and CXCL5 in regulating neutrophilic and type 2 responses in viral-induced asthma exacerbation is unknown. Inhibition of CXCL3 or CXCL5 with silencing RNAs in a mouse model of RV-induced exacerbation of asthma attenuated the accumulation of CXCR2+ neutrophils, eosinophils, and innate lymphoid cells in the lung and decreased production of type 2 regulatory factors IL-25, IL-33, IL-5, IL-13, CCL11, and CCL24. Suppression of inflammation was associated with decreased airways hyperreactivity, mucus hypersecretion, and collagen deposition. Similar results were obtained by employing RC-3095, which has been shown to bind to CXCR2, or by depletion of neutrophils. Our data demonstrate that CXCL3 and CXCL5 may be critical in the perpetuation of RV-induced exacerbation of asthma through the recruitment of CXCR2-positive neutrophils and by promoting type 2 inflammation. Targeting the CXCL3/CXCL5/CXCR2 axis may provide a new therapeutic approach to attenuating RV-induced exacerbations of asthma. |
| Databáze: | OpenAIRE |
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