{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T02:39:53Z","timestamp":1794019193773,"version":"4.8.0"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01ES037601, R56ES034386, T32ES029074, P30CA046934"],"award-info":[{"award-number":["R01ES037601, R56ES034386, T32ES029074, P30CA046934"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mast cells are abundant throughout the lung, positioned near the airway epithelium, vasculature, and interstitium where they function as frontline sentinels to inhaled environmental and chemical stimuli. Through rapid release of cytokines, proteases, and lipid mediators, they amplify inflammation, modulate vascular permeability, and shape the recruitment and activation of other immune cells. Although mast cells can influence dendritic cell (DC) positioning and function, their role in regulating DC dynamics during acute chemical-induced lung injury remains poorly defined. Chloropicrin (CP), a highly toxic pulmonary irritant and chemical threat agent, induces severe epithelial damage and inflammation, yet the mast cell\u2013dependent mechanisms governing these responses are not well understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      Two complementary mast cell\u2013deficient mouse models, cKit-dependent (Kit\n                      <jats:sup>W-sh<\/jats:sup>\n                      ) and cKit-independent (Cpa3-Cre; Mcl-1\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      ), were exposed to CP via oropharyngeal aspiration. Lung inflammation, tissue injury, and immune cell composition were assessed using bronchoalveolar lavage, histopathology, and multiparameter flow cytometry. Semi-targeted lipidomics was performed to evaluate mast cell\u2013dependent remodeling of pulmonary oxylipins.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CP exposure in wild-type mice caused pronounced alveolar disruption, vascular remodeling, and increased bronchoalveolar cellularity, whereas mast cell\u2013deficient mice exhibited attenuated inflammation and preserved lung structure. Mast cells critically regulated DC homeostasis: both cDC1 and cDC2 abundances were markedly elevated in mast cell\u2013deficient mice, while migration of each subset toward the pulmonary vasculature occurred in both genotypes. Lipidomic profiling revealed mast cell\u2013dependent alterations in oxylipins, including elevated leukotriene E\n                      <jats:sub>4<\/jats:sub>\n                      and depletion of linoleic acid\u2013derived mediators, identifying a lipid mediator signature associated with mast cell activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Mast cells orchestrate CP-induced lung injury by controlling inflammatory magnitude, dendritic cell abundance and persistence, and oxylipin signaling networks. These findings reveal a previously unrecognized mast cell\u2013dependent regulatory axis governing DC localization and resolution during chemical-induced pulmonary inflammation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1763509","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:18:59Z","timestamp":1777609139000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Mast cells shape early pulmonary inflammation and regulate dendritic cell abundance and localization after chemical induced lung injury"],"prefix":"10.3389","volume":"17","author":[{"given":"Matthew","family":"Gibb","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus","place":["Aurora, CO, United 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