ibd-associated tl1a gene (tnfsf15) haplotypes determine increased expression of tl1a proteinibd-associated tl1a基因(tnfsf15)单确定增加tl1a蛋白的表达.pdfVIP

IBD-Associated TL1A Gene (TNFSF15) Haplotypes Determine Increased Expression of TL1A Protein 1 1 2 1 2 1 Kathrin S. Michelsen , Lisa S. Thomas , Kent D. Taylor , Qi T. Yu , Ling Mei , Carol J. Landers , Carrie 1 1 2 1 Derkowski , Dermot P. B. McGovern , Jerome I. Rotter , Stephan R. Targan * 1 Inflammatory Bowel Disease Center Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America, 2 Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America Abstract Background: The recently identified member of the TNF superfamily TL1A (TNFSF15) increases IFN-c 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#0.001). CD14+ monocytes isolated from Jewish OmpC+ patients homozygous for TL1A gene haplotype B express higher levels of TL1A in response to FccR 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 patien