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Transcription Factor T-bet Attenuates the Development of Elastase-induced Emphysema in Mice
- Source :
- American Journal of Respiratory Cell and Molecular Biology
- Publication Year :
- 2019
- Publisher :
- American Thoracic Society, 2019.
-
Abstract
- Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by peripheral airways inflammation and emphysema. Emerging evidence indicates a contribution of both innate and adaptive immune cells to the development of COPD. Transcription factor T-bet modulates the function of immune cells and therefore might be involved in the pathogenesis of COPD. To elucidate the role for T-bet in elastase-induced emphysema, pathological phenotypes were compared between wild-type and T-bet-/- mice. T-bet-/- mice demonstrated enhanced emphysema development on histological analyses, with higher values of mean linear intercept and dynamic compliance relative to wild-type mice. The number of neutrophils in BAL fluids, lung IL-6 and IL-17 expression, and the proportion of CD4+ T cells positive for IL-17 or retinoic acid receptor-related orphan receptor-γt were higher in T-bet-/- mice than in wild-type mice. Although T-bet downregulates cytokine expression in bone marrow-derived macrophages and MH-S cells, a murine alveolar cell line, depending on the surrounding environment, IL-6 expression in alveolar macrophages isolated from elastase-treated mice was not dependent on T-bet. Coculture of bone marrow-derived macrophages and CD4+ T cells revealed that T-bet regulation of IL-17 expression was dependent on CD4+ T cells. Neutralizing antibodies against IL-6R or IL-17 ameliorated the development of emphysema in T-bet-/- mice. In conclusion, we demonstrate that T-bet ameliorates elastase-induced emphysema formation by modulating the host immune response in the lungs.
- Subjects :
- CD4-Positive T-Lymphocytes
0301 basic medicine
Neutrophils
Clinical Biochemistry
Adaptive Immunity
Pathogenesis
Mice
0302 clinical medicine
Medicine
RNA, Small Interfering
Lung
Mice, Knockout
Mice, Inbred BALB C
Pancreatic Elastase
biology
Elastase
Nuclear Receptor Subfamily 1, Group F, Member 1
hemic and immune systems
respiratory system
Chemotaxis, Leukocyte
Phenotype
medicine.anatomical_structure
Pulmonary Emphysema
Cytokines
Female
RNA Interference
Interleukin 17
medicine.symptom
Bronchoalveolar Lavage Fluid
Pulmonary and Respiratory Medicine
chemical and pharmacologic phenomena
Inflammation
Alveolar cells
03 medical and health sciences
Immune system
Animals
Interleukin 6
Molecular Biology
business.industry
Macrophages
Editorials
Cell Biology
Immunity, Innate
Lymphocyte Subsets
respiratory tract diseases
030104 developmental biology
030228 respiratory system
Immunology
biology.protein
T-Box Domain Proteins
business
Subjects
Details
- ISSN :
- 15354989 and 10441549
- Volume :
- 61
- Database :
- OpenAIRE
- Journal :
- American Journal of Respiratory Cell and Molecular Biology
- Accession number :
- edsair.doi.dedup.....981075f1c4eff4e4b12314b04b856ae6