HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER		Author Keyword(s) Vol Page [Advanced]

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sanders, D S A Search for Related Content PubMed PubMed Citation Articles by Sanders, D S A

Mucosal integrity and barrier function in the pathogenesis of early lesions in Crohn’s disease

Correspondence to:
Dr D S A Sanders
South Warwickshire General Hospitals NHS Trust, Department of Histopathology, Warwick Hospital, Lakin Road, Warwick CV34 5BW, UK; scott.sanders{at}swh.nhs.uk
ABSTRACT
Crohn’s disease aetiology is multifactorial and remains enigmatic. However, animal models show that disease heterogeneity is probable, in that more than one defective mucosal mechanism can produce the same clinical phenotype. For example, Crohn’s-like lesions are reported after compromise of mucosal integrity per se in the presence of an intact immune system, through altered expression of mucosal adhesion molecules, such as cadherins and tight junction proteins, highlighting the importance of the mucosal barrier in the disease process. Key to mucosal damage is the trigger of an inflammatory cascade after luminal antigen processing, a role classically ascribed to M cells in the surface follicle associated epithelium. Direct luminal antigen sampling has recently been proposed, however, by extension of dendritic cell (DC) processes through the intact gut epithelium, and it follows that early mucosal damage could result from de novo lymphoid recruitment. Cytokines, such as tumour necrosis factor (TNF), are known to drive inflammation, but emerging data suggest additional important roles for TNF influencing mucosal barrier efficacy by altering adhesion molecule expression, influencing epithelial apoptosis, and affecting tight junction functionality.

Abbreviations: DC, dendritic cells; FAE, follicle associated epithelium; GI, gastrointestinal; TNF, tumour necrosis factor

Keywords: Crohn’s; colitis; cadherin; tumour necrosis factor ; aphthoid; CARD15/NOD2

This article has been cited by other articles:

				L. Charrier-Hisamuddin, C. L. Laboisse, and D. Merlin ADAM-15: a metalloprotease that mediates inflammation FASEB J, March 1, 2008; 22(3): 641 - 653. [Abstract] [Full Text] [PDF]

				X. Sun, H. Yang, K. Nose, S. Nose, E. Q. Haxhija, H. Koga, Y. Feng, and D. H. Teitelbaum Decline in intestinal mucosal IL-10 expression and decreased intestinal barrier function in a mouse model of total parenteral nutrition Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G139 - G147. [Abstract] [Full Text] [PDF]

				L. Charrier, Y. Yan, H. T. T. Nguyen, G. Dalmasso, C. L. Laboisse, A. T. Gewirtz, S. V. Sitaraman, and D. Merlin ADAM-15/Metargidin Mediates Homotypic Aggregation of Human T Lymphocytes and Heterotypic Interactions of T Lymphocytes with Intestinal Epithelial Cells J. Biol. Chem., June 8, 2007; 282(23): 16948 - 16958. [Abstract] [Full Text] [PDF]

				P. Brun, I. Castagliuolo, V. D. Leo, A. Buda, M. Pinzani, G. Palu, and D. Martines Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis Am J Physiol Gastrointest Liver Physiol, February 1, 2007; 292(2): G518 - G525. [Abstract] [Full Text] [PDF]