Frontiers in immunology · 2026
Mast cells shape early pulmonary inflammation and regulate dendritic cell abundance and localization after chemical induced lung injury.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Gibb Matthew, Anderson Colin, Reinert Angela N, Schedin Troy, Boyd Jonathan, Reisz Julie A, Tewari-Singh Neera, Bauer Alison K, Brown Jared M
Аннотация
BACKGROUND: 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-dependent mechanisms governing these responses are not well understood.
MATERIALS AND METHODS: Two complementary mast cell-deficient mouse models, cKit-dependent (KitW-sh) and cKit-independent (Cpa3-Cre; Mcl-1fl/fl), 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-dependent remodeling of pulmonary oxylipins.
RESULTS: CP exposure in wild-type mice caused pronounced alveolar disruption, vascular remodeling, and increased bronchoalveolar cellularity, whereas mast cell-deficient 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-deficient mice, while migration of each subset toward the pulmonary vasculature occurred in both genotypes. Lipidomic profiling revealed mast cell-dependent alterations in oxylipins, including elevated leukotriene E4 and depletion of linoleic acid-derived mediators, identifying a lipid mediator signature associated with mast cell activity.
CONCLUSIONS: 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-dependent regulatory axis governing DC localization and resolution during chemical-induced pulmonary inflammation.
MATERIALS AND METHODS: Two complementary mast cell-deficient mouse models, cKit-dependent (KitW-sh) and cKit-independent (Cpa3-Cre; Mcl-1fl/fl), 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-dependent remodeling of pulmonary oxylipins.
RESULTS: CP exposure in wild-type mice caused pronounced alveolar disruption, vascular remodeling, and increased bronchoalveolar cellularity, whereas mast cell-deficient 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-deficient mice, while migration of each subset toward the pulmonary vasculature occurred in both genotypes. Lipidomic profiling revealed mast cell-dependent alterations in oxylipins, including elevated leukotriene E4 and depletion of linoleic acid-derived mediators, identifying a lipid mediator signature associated with mast cell activity.
CONCLUSIONS: 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-dependent regulatory axis governing DC localization and resolution during chemical-induced pulmonary inflammation.