{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:03:01Z","timestamp":1790168581382,"version":"4.1.0"},"reference-count":83,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003716","name":"Korea Basic Science Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003716","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Asthma exacerbations caused by human rhinovirus (hRV) infection are characterized by airway neutrophilia and reduced corticosteroid response, leading to significant healthcare costs and lung function impairment. The G\u03b1s subunit of the trimeric G protein regulates immunopathological conditions by modulating cAMP levels. We aimed to investigate the impact of myeloid cAMP levels on neutrophil\u2010dominated asthma exacerbation caused by hRV infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We generated mice with myeloid cell\u2010specific deletion of the G\u03b1s subunit by targeting the LysM gene, leading to a specific reduction of cAMP in myeloid cells. Neutrophilic asthma exacerbation was induced by hRV infection during allergen challenge, and cytokine production in BALF and lung tissue was assessed, along with histological examinations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Myeloid G\u03b1s ablation was found to shift airway inflammation from a neutrophilic to an eosinophilic phenotype during hRV\u2010induced asthma exacerbation. This change led to mucus hypersecretion and Th2\u2010type inflammation, and enhanced CD4\n                      <jats:sup>+<\/jats:sup>\n                      Th2 effector cell expansion. In chronic asthma with repeated allergen and hRV exposure, myeloid G\u03b1s ablation caused mixed Th2\u2010 and Th17\u2010biased inflammation with increased neutrophil and eosinophil infiltration and collagen deposition. Myeloid G\u03b1s deficiency hindered NLRP3 inflammasome activation, thereby suppressing M1 polarization of interstitial macrophages during eosinophilic inflammation. cAMP levels in macrophages were likely associated with M1 polarization, as cAMP analogs regulated NLRP3 inflammasome activation via PKA and EPAC pathways. Finally, adoptive transfer of cAMP analog\u2010treated macrophages reversed eosinophilic to neutrophilic inflammation in myeloid G\u03b1s\u2010ablated mice following hRV infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results highlight the essential role of macrophage cAMP in steroid\u2010resistant, neutrophil\u2010dominant airway inflammation during hRV\u2010induced asthma exacerbation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70018","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T07:06:43Z","timestamp":1756451203000},"page":"3055-3076","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Myeloid\n                    <scp>cAMP<\/scp>\n                    Reduction Shifts Rhinovirus\u2010Induced Airway Inflammation From Neutrophilic to Eosinophilic by Suppressing\n                    <scp>M1<\/scp>\n                    \u2010Interstitial Macrophages"],"prefix":"10.1111","volume":"80","author":[{"given":"Seong Ok","family":"Park","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Biosafety Research Institute and Core Facility Center for Zoonosis Research Jeonbuk National University  Iksan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erdenebileg","family":"Uyangaa","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Biosafety Research Institute and Core Facility Center for Zoonosis Research Jeonbuk National University  Iksan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Biosafety Research Institute and Core Facility Center for Zoonosis Research Jeonbuk National University  Iksan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Won","family":"Byeon","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Biosafety Research Institute and Core Facility Center for Zoonosis Research Jeonbuk National University  Iksan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Young","family":"Choi","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Biosafety Research Institute and Core Facility Center for Zoonosis Research Jeonbuk National University  Iksan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koanhoi","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine Pusan National University  Busan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy &amp; Immunology, Department of Medicine University of California, San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Bertin","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy &amp; Immunology, Department of Medicine University of California, San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyal","family":"Raz","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy &amp; Immunology, Department of Medicine University of California, San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Kug","family":"Eo","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Biosafety Research Institute and Core Facility Center for Zoonosis Research Jeonbuk National University  Iksan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-020-00785-1"},{"key":"e_1_2_11_3_1","unstructured":"Global Initiative for Asthma (GINA) \u201cGlobal Strategy for Asthma Management and Prevention \u201d(2021) https:\/\/ginasthma.org\/wp\u2010content\/uploads\/2021\/04\/GINA\u2010Main\u2010report\u20102021\u2010V2\u2010WMS.pdf."},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2016.04.011"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2013.5.4.189"},{"key":"e_1_2_11_6_1","first-page":"624","article-title":"Asthma Exacerbation: 1 Epidemiology","volume":"71","author":"Bateman E. 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