title: Transgenic modelling of cytokine polarization in the lung.
abstract: The lung is one of the commonest sites of exposure to environmental allergen or pathogen, so the expression of a variety of cytokines in the lung is dynamically regulated by inflammatory or structural cells in the lung. In the last decades, characterization of the local lung cytokine milieu in allergic or injury models has identified a collective role of certain cytokines, such as type 1 or type 2 cytokines, driving polarized inflammatory and tissue phenotypes. With the development of transgenic mouse modelling systems, the effector function of individual cytokine and the pathophysiological consequences of cytokine polarization in the lung have been effectively evaluated. Here, we present an overview of the transgenic systems currently used to assess the biological function of cytokine or other mediators in the lung. We discuss the inflammatory and tissue phenotypes detected in the lungs of transgenic mice over-expressing representative T helper type 1 (interferon-γ, interleukin-12), T helper type 2 (interleukins -4, -5, -9, -10 and -13), and T helper type 17 cytokines. The effects of genetic modification of cytokine receptors or transcriptional factors such as GATA-3 and T-bet in pulmonary inflammation and remodelling tissue responses are also discussed because these transcription factors are regarded as essential regulators of cytokine polarization. Finally, we discuss the limitations and future application of transgenic approaches in the studies of human lung diseases characterized by cytokine polarization.
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, Department of Internal Medicine, New Haven, CT 06520, USA.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Dela Cruz
authors.forename: Min-Jong
authors.initials: MJ
authors.lastname: Kang
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Cho
authors.forename: Chun Geun
authors.initials: CG
authors.lastname: Lee
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D007249:Inflammation; D008168:Lung / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D010641:Phenotype
chemical_list: D016207:Cytokines