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Epithelial ICAM-1 and ICAM-2 regulate the egression of human T cells across the bronchial epithelium

Porter, J.C.; Hall, A.; (2009) Epithelial ICAM-1 and ICAM-2 regulate the egression of human T cells across the bronchial epithelium. The FASEB Journal , 23 (2) pp. 492-502. 10.1096/fj.08-115899. Green open access

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Abstract

Egression of inflammatory cells from the lung interstitium into the airway lumen is critical for the resolution of inflammation, but the underlying mechanisms of this egression are unclear. Here, we use an in vitro system, in which human T cells migrate across a bronchial epithelial monolayer, to investigate the molecules involved. We show that although inhibition of T-cell LFA-1 blocks egression by 75 ! 5.6% (P<0.0001), inhibition of the LFA-1- ligand ICAM-1 on the epithelium only inhibits by 52.7 ! 0.06% (P"0.0001). We, therefore, looked for other epithelial ligands for LFA-1 and demonstrate that ICAM-2, but not ICAM-3, is expressed on the bronchial epithelium. Blocking ICAM-2 inhibits egression by 50.95 ! 10.79% (P"0.04), and blocking both ICAM-1 and ICAM-2 inhibits egression by 69.6 ! 5.2% (P< 0.0001). Inhibition of LFA-1/ICAM-1 and ICAM-2 interactions on the basolateral epithelium does not prevent egressing T cells from adhering, polarizing, or moving over the basal epithelium, but it does prevent their recognition of the interepithelial junctions. In conclusion, we show that egression of T cells involves three distinct sequential steps: adhesion, junctional recognition, and diapedesis; we further demonstrate that ICAM-2 is expressed on the bronchial epithelium and, together with ICAM-1, has an essential function in the clearance of T cells from the lung.—Porter, J. C., Hall, A. Epithelial ICAM-1 and ICAM-2 regulate the egression of human T cells across the bronchial epithelium. FASEB J. 23, 000–000 (2009)

Type: Article
Title: Epithelial ICAM-1 and ICAM-2 regulate the egression of human T cells across the bronchial epithelium
Open access status: An open access version is available from UCL Discovery
DOI: 10.1096/fj.08-115899
Publisher version: http://dx.doi.org/10.1096/fj.08-115899
Language: English
Keywords: Transepithelial migration, lymphocytes, LFA-1, lung, Neuronal Wiskott-Aldrich syndrome protein, coxsackie-adenovirus receptor
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/13873
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