Abstract | BACKGROUND: The recently identified member of the TNF superfamily TL1A (TNFSF15) increases IFN-gamma production by T cells in peripheral and mucosal CCR9+ T cells. TL1A and its receptor DR3 are up-regulated during chronic intestinal inflammation in ulcerative colitis and Crohn's disease (CD). TL1A gene haplotypes increase CD susceptibility in Japanese, European, and US cohorts. METHODOLOGY AND PRINCIPAL FINDINGS: Here we report that the presence of TL1A gene haplotype B increases risk in Jewish CD patients with antibody titers for the E. coli outer membrane porin C (OmpC+) (Haplotype B frequency in Jewish CD patients: 24.9% for OmpC negative and 41.9% for OmpC positive patients, respectively, P< or =0.001). CD14+ monocytes isolated from Jewish OmpC+ patients homozygous for TL1A gene haplotype B express higher levels of TL1A in response to FcgammaR stimulation, a known inducing pathway of TL1A, as measured by ELISA. Furthermore, the membrane expression of TL1A is increased on peripheral monocytes from Jewish but not non-Jewish CD patients with the risk haplotype. CONCLUSIONS AND SIGNIFICANCE: These findings suggest that TL1A gene variation exacerbates induction of TL1A in response to FcgammaR stimulation in Jewish CD patients and this may lead to chronic intestinal inflammation via overwhelming T cell responses. Thus, TL1A may provide an important target for therapeutic intervention in this subgroup of IBD patients.
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Authors | Kathrin S Michelsen, Lisa S Thomas, Kent D Taylor, Qi T Yu, Ling Mei, Carol J Landers, Carrie Derkowski, Dermot P B McGovern, Jerome I Rotter, Stephan R Targan |
Journal | PloS one
(PLoS One)
Vol. 4
Issue 3
Pg. e4719
( 2009)
ISSN: 1932-6203 [Electronic] United States |
PMID | 19262684
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Bacterial
- Escherichia coli Proteins
- OmpC protein
- Porins
- Receptors, IgG
- TNFSF15 protein, human
- Tumor Necrosis Factor Ligand Superfamily Member 15
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Topics |
- Antibodies, Bacterial
(blood)
- Crohn Disease
(ethnology, genetics)
- Escherichia coli Proteins
(immunology)
- Genetic Variation
- Genotype
- Haplotypes
- Humans
- Inflammatory Bowel Diseases
(genetics)
- Jews
- Porins
(immunology)
- Receptors, IgG
(physiology)
- Transcriptional Activation
- Tumor Necrosis Factor Ligand Superfamily Member 15
(analysis, genetics)
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