Loss of pro-apoptotic Bim promotes accumulation of pulmonary T lymphocytes and enhances allergen-induced goblet cell metaplasia

Pierce, J; Rir-Sima-Ah, J; Estrada, I; Wilder, J; Strasser, A; Tesfaigzi, Y

Author(s): Pierce, J; Rir-Sima-Ah, J; Estrada, I; Wilder, J; Strasser, A; Tesfaigzi, Y;
Details: Publication Year 2006-11,Volume 291,Issue #5,Page L862-L870
Journal Title: AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Publication Type: Journal Article
Abstract: 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 gamma delta 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 IFN gamma 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-13R alpha 2 was reduced in bim(-/-) mice compared with WT mice at 4 days. Furthermore, treatment of bronchiolar explant cultures with increasing IFN gamma levels reduced immunostaining for IL-13R alpha 2. Collectively, these studies suggest that, during prolonged exposure to allergen, Bim plays no role in the resolution of GCM, but increased IFN gamma levels in bim(-/-) mice may be responsible for reduced expression of IL-13R alpha 2 and enhanced GCM despite similar levels of IL-13 in bim(-/-) and bim(-/-) mice.
Publisher: AMER PHYSIOLOGICAL SOC
Keywords: FAMILY-MEMBER BIM; BH3-ONLY PROTEIN BIM; BROWN-NORWAY RATS; INDUCED AIRWAY HYPERREACTIVITY; PROAPOPTOTIC BCL-2 FAMILY; MURINE ASTHMA MODEL; IFN-GAMMA; TRANSCRIPTIONAL REGULATION; MOLECULAR-CLONING; CLARA CELLS
Publisher's Version: https://doi.org/10.1152/ajplung.00516.2005
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Creation Date: 2006-11-01 12:00:00