Authors: Hausding, Michael; Sauer, Kerstin; Maxeiner, Joachim H.; Finotto, Susetta

Source: Current Drug Targets, Volume 9, Number 6, June 2008 , pp. 503-510(8)

Publisher: Bentham Science Publishers

Abstract:

The immunoresponses are mediated by cells presenting the antigen to T cells. The transcription factors involved in the differentiation of T helper cells enclose T-bet (Th1), c-maf (Th2), GATA-3 (Th2), Foxp3 (T reg) and RORγT (Th17). They are regulated in allergic asthma. The use of murine models either as germline or as tissue specific transgenic mice has given decisive immunological tools to understand the importance of selected transcription factors or cytokines. Tissue specific transgenic lines have been generated into the Clara Cell or CD2 promoter directing tissue- and immune cells specific expression of the gene of interest. We identified T cell transcription factors important for asthma - such as T-bet, c-maf, GATA-3. Transgenic and knockout murine models of these transcription factors provided very important information for the human disease. Regarding to the pathogenesis of chronic asthma, we generated transgenic lines overexpressing IL-18 and analyzed a dominant negative mutant of the TGF-β receptor II. These models will offer to us a great input for the understanding of the T cell memory and the processes like airway remodelling. Beside DNA microinjection and stem cell transfer the On/Off systems like Cre-lox models have helped to understand the role of selected genes in different steps of experimental disease. Moreover, the transgenic model provide reliable models for the preclinical approval of therapy for allergic asthma to develop more efficient compounds and functional antibodies.

Keywords: Transgenic mice; allergic asthma; T regulatory cells; CD2 promoter; T-bet; TGF-β1

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138945008784533570

Publication date: 2008-06-01

More about this publication?

• Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.

Related content

• In this: publication
• By this: publisher
• In this Subject: Pharmacology
• By this author: Hausding, Michael ;  Sauer, Kerstin ;  Maxeiner, Joachim H. ;  Finotto, Susetta

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers