{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T12:03:47Z","timestamp":1790337827663,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001043","name":"Cass Foundation","doi-asserted-by":"publisher","award":["10466"],"award-info":[{"award-number":["10466"]}],"id":[{"id":"10.13039\/501100001043","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational All"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Severe asthma is a chronic inflammatory disease characterised by airway dysfunction, persistent immune activation and corticosteroid resistance. While macrophages are key regulators of lung immunity, how individual subsets, particularly interstitial macrophages (IMs), contribute to disease remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Lung macrophages were profiled using single\u2010cell RNA\u2010sequencing (scRNA\u2010seq) and flow cytometry in a C57BL\/6\u00a0mouse model of severe asthma induced by Complete Freund's Adjuvant (CFA) and house dust mite (HDM). Human transcriptomic data from the U\u2010BIOPRED asthma cohort were analyzed for translational validation. The dual CCR2\/CCR5 antagonist Cenicriviroc (CVC) was used to evaluate the therapeutic potential of targeting pathogenic macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CFA\u2010HDM treatment led to marked depletion of resident alveolar macrophages (rAMs) and their replacement by recruited AMs (recAMs) associated with tissue remodeling. A distinct Lyve1\n                      <jats:sup>lo<\/jats:sup>\n                      MHCII\n                      <jats:sup>hi<\/jats:sup>\n                      IM subset emerged as the dominant inflammatory cell population, displaying high\n                      <jats:italic>Ccr2<\/jats:italic>\n                      and\n                      <jats:italic>Ccr5<\/jats:italic>\n                      expression, potent pro\u2010inflammatory and antigen\u2010presenting signatures, and extensive ligand\u2013receptor communication with T cells, neutrophils and rAMs. Trajectory analysis demonstrated that both recAMs and Lyve1\n                      <jats:sup>lo<\/jats:sup>\n                      MHCII\n                      <jats:sup>hi<\/jats:sup>\n                      IMs arise from classical monocytes. Consistently, sputum transcriptomic data from the U\u2010BIOPRED asthma cohort showed reduced AM\u2010associated gene signatures and enrichment of IM\/monocyte and CCR\u2010chemokine programs in patients with severe disease. Pharmacological blockade of CCR2\/CCR5 with CVC markedly reduced IM infiltration, limited T\u2010cell and neutrophil recruitment, restored macrophage balance, and improved lung function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Lyve1\n                      <jats:sup>lo<\/jats:sup>\n                      MHCII\n                      <jats:sup>hi<\/jats:sup>\n                      IMs orchestrate airway inflammation in severe asthma. Dual CCR2\/CCR5 antagonism inhibits their recruitment, restores macrophage balance, and halts disease progression, highlighting this pathway as a promising therapeutic target.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/clt2.70201","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T19:10:37Z","timestamp":1789240237000},"source":"Crossref","is-referenced-by-count":0,"title":["CCR2\/CCR5 Signaling Defines a Pathogenic Interstitial Macrophage Subset That Drives Severe Asthma"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0901-5183","authenticated-orcid":false,"given":"Hao","family":"Wang","sequence":"first","affiliation":[{"name":"School of Health and Biomedical Sciences RMIT University  Melbourne Victoria Australia"},{"name":"Centre for Respiratory Science &amp; Health  Melbourne Victoria 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