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Transcription Factor T-bet Attenuates the Development of Elastase-induced Emphysema in Mice.
- Source :
- American Journal of Respiratory Cell & Molecular Biology; Oct2019, Vol. 61 Issue 4, p525-536, 12p
- Publication Year :
- 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<superscript>-/-</superscript> mice. T-bet<superscript>-/-</superscript> 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<superscript>+</superscript> T cells positive for IL-17 or retinoic acid receptor-related orphan receptor-gt were higher in T-bet<superscript>-/-</superscript>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<superscript>+</superscript> T cells revealed that T-bet regulation of IL-17 expression was dependent on CD4<superscript>+</superscript> T cells. Neutralizing antibodies against IL-6R or IL-17 ameliorated the development of emphysema in T-bet<superscript>-/-</superscript> mice. In conclusion, we demonstrate that T-bet ameliorates elastase-induced emphysema formation by modulating the host immune response in the lungs. [ABSTRACT FROM AUTHOR]
- Subjects :
- OBSTRUCTIVE lung diseases
LUNG diseases
PULMONARY emphysema
NEUTROPHILS
BONE marrow
Subjects
Details
- Language :
- English
- ISSN :
- 10441549
- Volume :
- 61
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- American Journal of Respiratory Cell & Molecular Biology
- Publication Type :
- Academic Journal
- Accession number :
- 138970145
- Full Text :
- https://doi.org/10.1165/rcmb.2018-0109OC