| First Author | Pierce J | Year | 2006 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 291 |
| Issue | 5 | Pages | L862-70 |
| PubMed ID | 16782750 | Mgi Jnum | J:121209 |
| Mgi Id | MGI:3709526 | Doi | 10.1152/ajplung.00516.2005 |
| Citation | Pierce J, et al. (2006) Loss of pro-apoptotic Bim promotes accumulation of pulmonary T lymphocytes and enhances allergen-induced goblet cell metaplasia. Am J Physiol Lung Cell Mol Physiol 291(5):L862-70 |
| abstractText | Immunological tolerance during prolonged exposure to allergen is accompanied by a shift in the lymphocyte content and a reduction of goblet cell metaplasia (GCM). Bim initiates negative selection of autoreactive T and B cells and shut down of T cell immune responses in vivo. The present study investigated whether Bim plays a role in the resolution of GCM during prolonged exposure to allergen. Loss of Bim increased T lymphocyte numbers in the bronchoalveolar lavage at 4 and 15 days of allergen exposure. The numbers of pulmonary CD4(+)8(-), CD4(-)8(+), and gammadelta T cells were significantly higher in naive and allergen-challenged bim(-/-) mice compared with wild-type (WT) littermates. When activated, pulmonary bim(-/-) T cells produced increased levels of IFNgamma compared with bim(+/+) T cells. No differences were noted in the total numbers of epithelial cells per millimeter of basal lamina between bim(+/+) and bim(-/-) mice, and the rate of resolution over 15 days of exposure was similar in both groups of mice. However, GCM was significantly enhanced and expression of IL-13Ralpha2 was reduced in bim(-/-) mice compared with WT mice at 4 days. Furthermore, treatment of bronchiolar explant cultures with increasing IFNgamma levels reduced immunostaining for IL-13Ralpha2. Collectively, these studies suggest that, during prolonged exposure to allergen, Bim plays no role in the resolution of GCM, but increased IFNgamma levels in bim(-/-) mice may be responsible for reduced expression of IL-13Ralpha2 and enhanced GCM despite similar levels of IL-13 in bim(+/+) and bim(-/-) mice. |
