Transgenic modelling of cytokine polarization in the lung

Abstract

SummaryThe 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-c, 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.

Nanomedicine-based co-delivery of a calcium channel inhibitor and a small molecule targeting CD47 for lung cancer immunotherapy

“…1, Supplementary Figs. 32,33). LRT treatment in vitro has been demonstrated to inhibit calcium influx and subsequently induce ER stress, resulting in the calreticulin upregulation and CD47 protein down-regulation in cancer cells.…”

“…Cytokines are essential in the host defense against invading pathogens as the products of immune signaling activation. The secretion of cytokines and related immune response constitutes the fundamentals of host defense, and tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interferon-γ (IFN-γ), and interleukin-6 (IL-6) are the predominant cytokines of innate immunity in the protection against a majority of lung diseases 33 . it has been widely reported that M1 polarization of macrophages is essential in the antitumor immune response, and various kinds of cytokines secreted by macrophages play dominant roles in regulating intracellular communication and killing cancer cells 34 .…”