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Expression of miR-223-3p was measured in lung tissue of two independent cohorts with patients with GOLD stage II\u2013IV COPD, never smokers, and smokers without COPD. The functional role of miR-223-3p was studied in deficient mice and on overexpression in airway epithelial cells from COPD and controls. We observed higher miR-223-3p levels in patients with COPD stage II\u2013IV compared with (non)-smoking controls, and levels were associated with higher neutrophil numbers in bronchial biopsies of patients with COPD. MiR-223-3p expression was also increased in lungs and bronchoalveolar lavage of cigarette smoke (CS)-exposed mice. CS-induced neutrophil and monocyte lung infiltration was stronger in miR-223-deficient mice on acute (5 days) exposure, but attenuated on subchronic (4 wk) exposure. Additionally, miR-223 deficiency attenuated acute and subchronic CS-induced lung infiltration of dendritic cells and T lymphocytes. Finally, in vitro overexpression of miR-223-3p in non-COPD airway epithelial cells suppressed C-X-C motif chemokine ligand 8 (CXCL8) and granulocyte monocyte-colony stimulation factor (GM-CSF) secretion and gene expression of the proinflammatory transcription factor TRAF6. Importantly, this suppressive effect of miR-223-3p was compromised in COPD-derived cultures. In conclusion, we demonstrate that miR-223-3p is increased in lungs of patients with COPD and CS-exposed mice and is associated with neutrophilic inflammation. In vivo data indicate that miR-223 acts as negative regulator of acute CS-induced neutrophilic and monocytic inflammation. In vitro data suggest that miR-223-3p does so by suppressing proinflammatory airway epithelial responses, which is less effective in COPD epithelium.<\/jats:p>","DOI":"10.1152\/ajplung.00252.2021","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T11:38:21Z","timestamp":1634729901000},"page":"L1091-L1104","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["MiR-223 is increased in lungs of patients with COPD and modulates cigarette smoke-induced pulmonary inflammation"],"prefix":"10.1152","volume":"321","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6805-2593","authenticated-orcid":true,"given":"Mirjam P.","family":"Roffel","sequence":"first","affiliation":[{"name":"Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, University 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