Journal ArticleDOI
Defective epithelial barrier function in asthma.
Chang Xiao,Sarah M. Puddicombe,Sarah A. Field,Joel Haywood,Victoria Broughton-Head,Ilaria Puxeddu,Hans Michael Haitchi,Elizabeth Vernon-Wilson,David Sammut,Nicole Bedke,Catherine Cremin,Jody Sones,Ratko Djukanovic,Peter H. Howarth,Jane E. Collins,Stephen T. Holgate,Phillip Monk,Donna E. Davies +17 more
TLDR
The results show that the bronchial epithelial barrier in asthma is compromised, which may facilitate the passage of allergens and other agents into the airway tissue, leading to immune activation and may thus contribute to the end organ expression of asthma.Abstract:
Background Asthma is a complex disease involving gene and environment interactions. Although atopy is a strong predisposing risk factor for asthma, local tissue susceptibilities are required for disease expression. The bronchial epithelium forms the interface with the external environment and is pivotally involved in controlling tissue homeostasis through provision of a physical barrier controlled by tight junction (TJ) complexes. Objectives To explain the link between environment exposures and airway vulnerability, we hypothesized that epithelial TJs are abnormal in asthma, leading to increased susceptibility to environmental agents. Methods Localization of TJs in bronchial biopsies and differentiated epithelial cultures was assessed by electron microscopy or immunostaining. Baseline permeability and the effect of cigarette smoke and growth factor were assessed by measurement of transepithelial electrical resistance and passage of fluorescently labeled dextrans. Results By using immunostaining, we found that bronchial biopsies from asthmatic subjects displayed patchy disruption of TJs. In differentiated bronchial epithelial cultures, TJ formation and transepithelial electrical resistance were significantly lower ( P P P Conclusions Our results show that the bronchial epithelial barrier in asthma is compromised. This defect may facilitate the passage of allergens and other agents into the airway tissue, leading to immune activation and may thus contribute to the end organ expression of asthma.read more
Citations
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Journal ArticleDOI
TEER Measurement Techniques for In Vitro Barrier Model Systems
Balaji Srinivasan,Aditya Reddy Kolli,Mandy B. Esch,Hasan E. Abaci,Michael L. Shuler,James J. Hickman +5 more
TL;DR: The aim of this article is to review the different TEER measurement techniques and analyze their strengths and weaknesses, determine the significance of TEER in drug toxicity studies, and examine the various in vitro models and microfluidic organs-on-chips implementations using TEER measurements in some widely studied barrier models.
Journal ArticleDOI
Innate and adaptive immune responses in asthma
TL;DR: Recent advances in understanding of the sentinel role played by innate immunity provides new targets for disease prevention and treatment that include pathways of innate stimulation by environmental or endogenous pathogen-associated molecular patterns (PAMPs) and danger-associated Molecular patterns (DAMPs), and the identification of new T cell subsets and lymphoid cells.
Journal ArticleDOI
The airway epithelium in asthma
Bart N. Lambrecht,Hamida Hammad +1 more
TL;DR: Improved understanding of the epithelium's function in maintaining the integrity of the airways and its dysfunction in asthma has provided important mechanistic insight into how asthma is initiated and perpetuated and could provide a framework by which to select new therapeutic strategies that prevent exacerbations and alter the natural course of the disease.
Journal ArticleDOI
Barrier Epithelial Cells and the Control of Type 2 Immunity
TL;DR: The general mechanisms of how different stimuli trigger type-2-cell-mediated immunity at mucosal barriers are reviewed and how this leads to protection or disease are reviewed.
Journal ArticleDOI
Unjamming and cell shape in the asthmatic airway epithelium
Jin-Ah Park,Jae Hun Kim,Dapeng Bi,Jennifer A. Mitchel,Nader Taheri Qazvini,Nader Taheri Qazvini,Kelan G. Tantisira,Chan Young Park,Maureen McGill,Sae Hoon Kim,Bomi Gweon,Jacob Notbohm,Robert L. Steward,Stephanie Burger,Scott H. Randell,Alvin T. Kho,Dhananjay T. Tambe,Dhananjay T. Tambe,C. Corey Hardin,Stephanie A. Shore,Elliot Israel,David A. Weitz,Daniel J. Tschumperlin,Elizabeth P. Henske,Scott T. Weiss,M. Lisa Manning,James P. Butler,Jeffrey M. Drazen,Jeffrey J. Fredberg +28 more
TL;DR: Cell shape provides a rigorous structural signature for classification and investigation of bronchial epithelial layer jamming in asthma, and potentially in any process in disease or development in which epithelial dynamics play a prominent role.
References
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Intestinal mucosal barrier function in health and disease.
TL;DR: Recent advances have uncovered mechanisms by which the intestinal mucosal barrier is regulated in response to physiological and immunological stimuli, along with evidence that this regulation shapes mucosal immune responses in the gut and, when dysfunctional, may contribute to disease.
Journal ArticleDOI
Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis
Colin N. A. Palmer,Alan D. Irvine,Ana Terron-Kwiatkowski,Yiwei Zhao,Haihui Liao,Simon P. Lee,David Goudie,Aileen Sandilands,Linda E. Campbell,Frances J.D. Smith,Grainne M. O'Regan,Rosemarie Watson,Jo E Cecil,Sherri J. Bale,John G. Compton,John J. DiGiovanna,John J. DiGiovanna,Philip Fleckman,Sue Lewis-Jones,Gehan Arseculeratne,Ann Sergeant,Colin S. Munro,Brahim El Houate,Ken McElreavey,Liselotte Brydensholt Halkjaer,Hans Bisgaard,Somnath Mukhopadhyay,Somnath Mukhopadhyay,W.H. Irwin McLean +28 more
TL;DR: It is shown that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis.
Journal ArticleDOI
Physiology and Function of the Tight Junction
James M. Anderson,Van Itallie Cm +1 more
TL;DR: Current information suggests that the paracellular barrier is most usefully modeled as having two physiologic components: a system of charge-selective small pores, 4 A in radius, and a second pathway created by larger discontinuities in the barrier, lacking charge or size discrimination.
Journal ArticleDOI
Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions
Hong Wan,Helen L Winton,Christian Soeller,Euan R. Tovey,Dieter C. Gruenert,Philip J. Thompson,Geoffrey A. Stewart,Graham W. Taylor,David R. Garrod,Mark B. Cannell,Clive Robinson +10 more
TL;DR: The results suggest that opening of TJs by environmental proteinases may be the initial step in the development of asthma to a variety of allergens.
Journal ArticleDOI
Tight junction defects in patients with atopic dermatitis.
Anna De Benedetto,Nicholas Rafaels,Laura Y. McGirt,Andrei I. Ivanov,Steve N. Georas,Chris Cheadle,Alan E. Berger,Kunzhong Zhang,Sadasivan Vidyasagar,Takeshi Yoshida,Mark Boguniewicz,Tissa Hata,Lynda C. Schneider,Jon M. Hanifin,Richard L. Gallo,Natalija Novak,Stephan Weidinger,Terri H. Beaty,Donald Y.M. Leung,Kathleen C. Barnes,Lisa A. Beck +20 more
TL;DR: It is suggested that an impairment in tight junctions contributes to the barrier dysfunction and immune dysregulation observed in AD subjects and that this may be mediated in part by reductions in claudin-1.