TL1A/DR3 interaction is associated with pathogenesis of inflammatory bowel disease in adults and children
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1
Medical University of Gdansk, Department of Histology, Poland
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2
Medical University of Lublin, Department of Gastroenterology with Endoscopic Unit, Poland
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3
Medical Univesrity of Gdansk, Department of Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition, Poland
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4
Medical University of Lublin, Department of Clinical Immunology, Poland
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5
Medical University of Gdansk, Department of Gastroenterology and Hepatology, Poland
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6
University of Warmia and Mazury, Department of Human Histology and Embryology, Poland
TL1A is a proinflammatory cytokine and the ligand for death receptor 3 (DR3). These proteins are strongly up-regulated on activated cells of the immune system. TL1A/DR3 interaction costimulates T-cells and induces production of several proinflammatory cytokines (including IL-4, IL-13, IL-17A, IFN-γ) by these cells. TL1A and DR3 are linked to the development of Crohn’s disease (CD) and ulcerative colitis (UC), although their exact pathological role remains unknown. In this study, we investigated the mRNA level of TL1A, IL-4, IL-13, IL-17A and IFN-γ in colon mucosal biopsies of paediatric and adult inflammatory bowel disease (IBD) patients. We found that expression of TL1A was significantly elevated in inflamed but not in non-inflamed colonic tissue of both CD and UC patients as compared to healthy individuals. Interestingly, we detected up-regulation of DR3 only in inflamed colonic tissue of paediatric but not adult patients. Up-regulation of TL1A mRNA was accompanied by elevated expression of proinflammatory cytokines and positively correlated with the expression level of IL-17A mRNA in inflamed and non-inflamed tissue of both paediatric and adult UC patients. Furthermore, TL1A and DR3 protein expression was localized by immunohistochemical technique not only to mucosa-infiltrating mononuclear cells but also to enterocytes. Our study also provides evidence for the first time that TL1A mRNA expression is significantly higher while DR3 mRNA expression is significantly lower in healthy adults compared to healthy children. These findings show that TL1A
contributes to the development of IBD via induction of IL-17A expression and this observation may have therapeutic implications.
Keywords:
TL1A,
inflammatory bowel disease,
DR3,
TNFSF15,
Inflammation,
IL17A
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Slebioda
TJ,
Wierzbicki
PM,
Stanislawowski
M,
Celinski
K,
Landowski
P,
Kaminska
B,
Bojarska-Junak
A,
Rolinski
J,
Adrych
K and
Kmiec
Z
(2013). TL1A/DR3 interaction is associated with pathogenesis of inflammatory bowel disease in adults and children.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00153
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Received:
11 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Tomasz J Slebioda, Medical University of Gdansk, Department of Histology, Gdansk, Poland, t.slebioda@gumed.edu.pl