The activating protein 1 transcription factor basic leucine zipper transcription factor, ATF-like (BATF), regulates lymphocyte- and mast cell-driven immune responses in the setting of allergic asthma

Ubel C, Sopel N, Graser A, Hildner K, Reinhardt C, Zimmermann T, Rieker RJ, Maier A, Neurath M, Murphy KM, Finotto S (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Publisher: Elsevier

Book Volume: 133

Pages Range: 198-206.e9

Journal Issue: 1

DOI: 10.1016/j.jaci.2013.09.049

Abstract

Mice without the basic leucine zipper transcription factor, ATF-like (BATF) gene (Batf(-/-)) lack TH17 and follicular helper T cells, which demonstrates that Batf is a transcription factor important for T- and B-cell differentiation.In this study we examined whether BATF expression would influence allergic asthma.In a cohort of preschool control children and children with asthma, we analyzed BATF mRNA expression using real-time PCR in PBMCs. In a murine model of allergic asthma, we analyzed differences in this allergic disease between wild-type, Batf transgenic, and Batf(-/-) mice.In the absence of corticosteroid treatment, children with recurrent asthma have a significant increase in BATF mRNA expression in their PBMCs. Batf(-/-) mice display a significant reduction in the pathophysiologic responses seen in asthmatic wild-type littermates. Moreover, we discovered a decrease in IL-3 production and IL-3-dependent mast cell development in Batf(-/-) mice. By contrast, IFN-? was induced in lung CD4(+) and CD8(+) T cells. Intranasal delivery of anti-IFN-? antibodies induced airway hyperresponsiveness and inflammation in wild-type but not in Batf(-/-) mice. Transgenic overexpression of Batf under the control of the CD2 promoter/enhancer augmented lung inflammation and IgE levels in the setting of experimental asthma.BATF is increased in non-steroid-treated asthmatic children. Targeting BATF expression resulted in amelioration of the pathophysiologic responses seen in children with allergic asthma, and BATF has emerged as a novel target for antiasthma interventions.

Authors with CRIS profile

Involved external institutions

Washington University United States (USA) (US)

How to cite

APA:

Ubel, C., Sopel, N., Graser, A., Hildner, K., Reinhardt, C., Zimmermann, T.,... Finotto, S. (2014). The activating protein 1 transcription factor basic leucine zipper transcription factor, ATF-like (BATF), regulates lymphocyte- and mast cell-driven immune responses in the setting of allergic asthma. Journal of Allergy and Clinical Immunology, 133(1), 198-206.e9. https://doi.org/10.1016/j.jaci.2013.09.049

MLA:

Ubel, Caroline, et al. "The activating protein 1 transcription factor basic leucine zipper transcription factor, ATF-like (BATF), regulates lymphocyte- and mast cell-driven immune responses in the setting of allergic asthma." Journal of Allergy and Clinical Immunology 133.1 (2014): 198-206.e9.

BibTeX: Download