Unique role of junctional adhesion molecule-a in maintaining mucosal homeostasis in inflammatory bowel disease.

  title={Unique role of junctional adhesion molecule-a in maintaining mucosal homeostasis in inflammatory bowel disease.},
  author={Stefania Vetrano and Maria Rescigno and Maria Rosaria Cera and Carmen Correale and Cristiano Rumio and Andrea Doni and Massimo Claudio Fantini and Andreas Sturm and Elena Monica Borroni and Alessandro Repici and Massimo Locati and Alberto Malesci and Elisabetta Dejana and Silvio Danese},
  volume={135 1},
BACKGROUND & AIMS Junctional adhesion molecule-A (JAM-A) is localized at the tight junctions and controls leukocyte migration into the tissues. However, its functional role in inflammatory bowel disease (IBD) is unexplored. METHODS Control, Crohn's disease (CD), and ulcerative colitis (UC) tissue specimens were studied for JAM-A expression, as well as the colon of mice given dextran sodium sulfate (DSS). Wild-type and JAM-A(-/-), Tie-2-Cre-JAM-A(-/-) (endothelial/hematopoietic-specific JAM… 

Figures from this paper

Targeted epithelial tight junction dysfunction causes immune activation and contributes to development of experimental colitis.

Primary pathophysiologically relevant intestinal epithelial barrier dysfunction is insufficient to cause experimental intestinal disease but can broadly activate mucosal immune responses and accelerate the onset and severity of immune-mediated colitis.

Function of the intestinal epithelium and its dysregulation in inflammatory bowel disease

This review focuses on recent developments in the structure of the epithelium, including a detailed account of the apical junctional complex in addition to the role of the enterocyte in antigen recognition, uptake, processing, and presentation.

JAM-related proteins in mucosal homeostasis and inflammation

The current knowledge regarding the roles of the JAM family members in the regulation of mucosal homeostasis and leukocyte trafficking is summarized with a particular emphasis on barrier function and its perturbation during pathological inflammation.

The Role of JAM‐A in Inflammatory Bowel Disease: Unrevealing the Ties That Bind

The role of JAM‐A is focused on in controlling mucosal homeostasis by regulating the integrity and permeability of epithelial barrier function, which is important in the pathogenesis of inflammatory bowel disease.

DICAM Attenuates Experimental Colitis via Stabilizing Junctional Complex in Mucosal Barrier.

This study demonstrates that DICAM which is increased in an inflammatory condition has a protective role in experimental colitis by stabilizing the integrity of junctional complex in the intestinal mucosal barrier.

Understanding the Epithelial Barrier in IBD

Tight junction dysregulation may play a central role in inflammatory bowel disease by linking mucosal immune responses to barrier function and triggering a recurrent cycle of barrier dysfunction and inflammation.

Glycoprotein A33 deficiency: a new mouse model of impaired intestinal epithelial barrier function and inflammatory disease

It is shown that GPA33, an intestine-specific cell surface protein, plays a role in the maintenance of intestinal barrier function and the prevention of intestinal pathologies such as food hypersensitivity, inflammatory bowel disease and colitis-associated cancer.

Inflammation-induced Occludin Downregulation Limits Epithelial Apoptosis by Suppressing Caspase 3 Expression.

Reduced levels of occludin and CASP3 in intestinal epithelial cells of patients with inflammatory bowel diseases might promote restoration of mucosal homeostasis in response to inflammatory conditions.

TNFR2 activates MLCK-dependent tight junction dysregulation to cause apoptosis-mediated barrier loss and experimental colitis.

In immune-mediated inflammatory bowel disease models, TNFR2 signaling increases long MLCK expression, resulting in tight junction dysregulation, barrier loss, and induction of colitis, which indicates that disease progresses via apoptosis in the absence of M LCK-dependent tight junction regulation.

Differential expression of junctional adhesion molecules in different stages of systemic sclerosis.

It is indicated that JAMs may participate in MVEC activation, inflammatory processes, and impaired angiogenesis in different stages of SSc.



JAM-A regulates permeability and inflammation in the intestine in vivo

A complex role is demonstrated in intestinal homeostasis by regulating epithelial permeability, inflammation, and proliferation by regulating Junctional Adhesion Molecule (JAM-A) within the tight junction.

Crucial role of the protein C pathway in governing microvascular inflammation in inflammatory bowel disease.

In isolated human intestinal endothelial cells, administration of recombinant activated PC had a potent antiinflammatory effect, as demonstrated by downregulated cytokine-dependent cell adhesion molecule expression and chemokine production as well as inhibited leukocyte adhesion to the inflamed intestinal vessels.

Increased DC trafficking to lymph nodes and contact hypersensitivity in junctional adhesion molecule-A-deficient mice.

A novel, non-redundant role of JAM-A is identified in controlling DC motility, trafficking to lymph nodes, and activation of specific immunity.

Angiogenesis as a novel component of inflammatory bowel disease pathogenesis.

Results provide morphological, phenotypic and functional evidence of potent angiogenic activity in both CD and UC mucosa, indicating that the local microvasculature undergoes an intense process of inflammation-dependent angiogenesis.

The role of junctional adhesion molecules in vascular inflammation

This Review summarizes recent progress and future directions in understanding the role of JAMs as 'gate keepers' in inflammation and vascular pathology.

Junctional adhesion molecule-A-deficient polymorphonuclear cells show reduced diapedesis in peritonitis and heart ischemia-reperfusion injury.

  • M. CoradaS. Chimenti E. Dejana
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 2005
It is reported that JAM-A is required for the correct infiltration of polymorphonuclear leukocytes (PMN) into an inflamed peritoneum or in the heart upon ischemia-reperfusion injury.

Proinflammatory Cytokines Disrupt Epithelial Barrier Function by Apoptosis-Independent Mechanisms 1

These findings for the first time clearly separate the proapoptotic effects of IFN-γ and TNF-α from their abilities to disrupt barrier function.

Junctional adhesion molecule-A deficiency increases hepatic ischemia-reperfusion injury despite reduction of neutrophil transendothelial migration.

It is shown for the first time that JAM-A is up-regulated in hepatic venules and serves as an endothelial receptor of neutrophil transmigration, but it does not mediate leukocyte rolling, adhesion, or platelet-endothelial cell interactions.

Angiogenesis blockade as a new therapeutic approach to experimental colitis

Active angiogenesis occurs in the gut of IL10−/− and DSS-treated colitic mice and parallels disease progression and provides the rational basis for considering anti-angiogenic strategies in the treatment of IBD in humans.