- Title
- 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
- Creator
- Sokulsky, Leon A; Garcia-Netto, Keilah; Foster, Paul S.; Nguyen, Thi Hiep; Girkin, Jason L. N.; Collison, Adam; Mattes, Joerg; Kaiko, Gerard; Liu, Chi; Bartlett, Nathan W.; Yang, Ming
- Relation
- NHMRC.1120696 http://purl.org/au-research/grants/nhmrc/1120696
- Relation
- Journal of Immunology Vol. 205, Issue 9, p. 2468-2478
- Publisher Link
- http://dx.doi.org/10.4049/jimmunol.1901350
- Publisher
- American Association of Immunologists
- Resource Type
- journal article
- Date
- 2020
- Description
- 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.
- Subject
- rhinovirus (RV); asthmatic; CXCL3; CXCL5; CXCR2; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1437284
- Identifier
- uon:40298
- Identifier
- ISSN:0022-1767
- Language
- eng
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