| First Author | Hayashi S | Year | 2019 |
| Journal | Am J Respir Cell Mol Biol | Volume | 61 |
| Issue | 4 | Pages | 525-536 |
| PubMed ID | 30965014 | Mgi Jnum | J:325271 |
| Mgi Id | MGI:6460210 | Doi | 10.1165/rcmb.2018-0109OC |
| Citation | Hayashi S, et al. (2019) Transcription Factor T-bet Attenuates the Development of Elastase-induced Emphysema in Mice. Am J Respir Cell Mol Biol 61(4):525-536 |
| abstractText | 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-gammat 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. |
