IL-4R and CXCR2 Contribute to Downregulating Neutrophil-Mediated Response in the Early Stage of Fungal Extract-Induced Allergic Airway Inflammation

• Published in: Biomedicines 2024-11, Vol.12 (12), p.2743
• Main Authors: Shevchenko, Marina A, Servuli, Ekaterina A, Murova, Dina E, Vavilova, Julia D, Bolkhovitina, Elena L, Chursanova, Ekaterina N, Sapozhnikov, Alexander M
• Format: Article
• Language: English
• Subjects: allergic airway inflammation; Allergies; Antigens; Aspergillus fumigatus extract; Asthma; Bacterial infections; Blood; Bone marrow; Bronchus; CD18 antigen; Chemokines; Cloning; CXCL1; CXCR2 protein; Cytokines; eosinophils; Ethylenediaminetetraacetic acid; Granulocytes; Health aspects; IL-4; Immune response; Inflammation; Inhalation; Interleukin 4; Laboratory animals; Lavage; Leukocytes (eosinophilic); Leukocytes (neutrophilic); Lymphocytes T; Neutrophils; Pathogenesis; Respiratory tract diseases
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines12122743

: Airborne exogenous antigen inhalation can induce neutrophil infiltration of the airways, while eosinophils migrate to the airways in allergic airway inflammation. During a bacterial infection, Th2-associated cytokine IL-4, by binding to the IL-4 receptor (IL-4R), can suppress neutrophil recruitment to the site of inflammation. In the present study, we estimated whether the IL-4-dependent suppression of neutrophil recruitment contributed to the development of an immune response in asthma. : Using a mouse model of extract-induced allergic airway inflammation, we investigated the proportions of eosinophils and neutrophils in blood, lungs, and bone marrow over time. Bronchoalveolar lavage (BAL) fluid cytokine (including IL-4) levels and the proportions of bone marrow IL-4Rα (CD124)-expressing neutrophils were estimated. : We identified skewing from the neutrophil- to eosinophil-mediated immune response in the blood after five extract applications. At this point, the BAL fluid IL-4 level was not elevated, while IL-12p40 and CXCL1 levels were considerably increased. At the early stage of allergic airway inflammation, the proportions of neutrophils expressing CD124 and circulating neutrophils expressing CXCR2 (CD182) were significantly increased. Upon inflammation progression, the former remained elevated, but the latter significantly decreased. : Thus, in allergic airway inflammation, bone marrow neutrophils become insensible to the attractive chemokine CXCL1 signals and susceptible to IL-4 effects.