{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:57:50Z","timestamp":1791183470933,"version":"4.1.0"},"reference-count":82,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The T cell Ig and mucin domain\u2013containing molecule (TIM) family of receptors have emerged as potential therapeutic targets to correct abnormal immune function in chronic inflammatory conditions. TIM-3 serves as a functional receptor in structural cells of the airways and via the ligand galectin-9 (Gal-9) can modulate the inflammatory response. The aim of this study was to investigate TIM-3 expression and function in neutrophils, focusing on its potential role in cystic fibrosis (CF) lung disease. Results revealed that TIM-3 mRNA and protein expression values of circulating neutrophils were equal between healthy controls (n = 20) and people with CF (n = 26). TIM-3 was detected on resting neutrophil membranes by FACS analysis, and expression levels significantly increased post IL-8 or TNF-\u03b1 exposure (p &amp;lt; 0.05). Our data suggest a novel role for TIM-3\/Gal-9 signaling involving modulation of cytosolic calcium levels. Via TIM-3 interaction, Gal-9 induced neutrophil degranulation and primed the cell for enhanced NADPH oxidase activity. Killing of Pseudomonas aeruginosa was significantly increased upon bacterial opsonization with Gal-9 (p &amp;lt; 0.05), an effect abrogated by blockade of TIM-3 receptors. This mechanism appeared to be Gram-negative bacteria specific and mediated via Gal-9\/ LPS binding. Additionally, we have demonstrated that neutrophil TIM-3\/Gal-9 signaling is perturbed in the CF airways due to proteolytic degradation of the receptor. In conclusion, results suggest a novel neutrophil defect potentially contributing to the defective bacterial clearance observed in the CF airways and suggest that manipulation of the TIM-3 signaling pathway may be of therapeutic value in CF, preferably in conjunction with antiprotease treatment.<\/jats:p>","DOI":"10.4049\/jimmunol.1300711","type":"journal-article","created":{"date-parts":[[2014,1,30]],"date-time":"2014-01-30T05:20:55Z","timestamp":1391059255000},"page":"2418-2431","source":"Crossref","is-referenced-by-count":52,"title":["Galectin-9 Signaling through TIM-3 Is Involved in Neutrophil-Mediated Gram-Negative Bacterial Killing: An Effect Abrogated within the Cystic Fibrosis Lung"],"prefix":"10.1093","volume":"192","author":[{"given":"Isabel","family":"Vega-Carrascal","sequence":"first","affiliation":[{"name":"Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital , Dublin 9,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Bergin","sequence":"additional","affiliation":[{"name":"Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital , Dublin 9,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver J","family":"McElvaney","sequence":"additional","affiliation":[{"name":"Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital , Dublin 9,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cormac","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital , Dublin 9,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nessa","family":"Banville","sequence":"additional","affiliation":[{"name":"Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital , Dublin 9,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Pohl","sequence":"additional","affiliation":[{"name":"Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital , Dublin 9,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuomi","family":"Hirashima","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University , Kagawa 761-0793,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay K","family":"Kuchroo","sequence":"additional","affiliation":[{"name":"Center for Neurologic Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emer P","family":"Reeves","sequence":"additional","affiliation":[{"name":"Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital , Dublin 9,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel G","family":"McElvaney","sequence":"additional","affiliation":[{"name":"Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital , Dublin 9,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,3,1]]},"reference":[{"key":"2025032404163354300_r1","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1164\/rccm.200304-505SO","article-title":"Pathophysiology and management of pulmonary infections in cystic fibrosis","volume":"168","author":"Gibson","year":"2003","journal-title":"Am. 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