TNF-like 1A (TL1A) is a newly described member of the TNF superfamily that is directly implicated in the pathogenesis of autoimmune diseases, including inflammatory bowel disease, atherosclerosis, and rheumatoid arthritis. We report the crystal structure of the human TL1A extracellular domain at a resolution of 2.5 A, which reveals a jelly-roll fold typical of the TNF superfamily. This structural information, in combination with complementary mutagenesis and biochemical characterization, provides insights into the binding interface and the specificity of the interactions between TL1A and the DcR3 and DR3 receptors. These studies suggest that the mode of interaction between TL1A and DcR3 differs from other characterized TNF ligand/receptor complexes. In addition, we have generated functional TL1A mutants with altered disulfide bonding capability that exhibit enhanced solution properties, which will facilitate the production of materials for future cell-based and whole animal studies. In summary, these studies provide insights into the structure and function of TL1A and provide the basis for the rational manipulation of its interactions with cognate receptors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790920 | PMC |
| http://dx.doi.org/10.1021/bi900031w | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Study on serum TL1A levels and their correlation with Th17 cells, IL-17 and IL-21 in children with Graves' disease.
Front Immunol
December 2024
Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Objective: To investigate serum TL1A levels and their correlation with Th17 cells, IL-17, and IL-21 in children with Graves' disease (GD).
Methods: Thirty-seven children (12 males and 25 females) aged 9-14 years with newly diagnosed and untreated GD were enrolled in this study. Serum TL1A, IL-17, and IL-21 levels were measured using enzyme-linked immunosorbent assay (ELISA).
Mechanisms of Insulin Signaling as a Potential Therapeutic Method in Intestinal Diseases.
Cells
November 2024
Institute of Medicine, Medical College of Rzeszow University, 35-959 Rzeszow, Poland.
Gastrointestinal diseases are becoming a growing public health problem. One of them is inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). The incidence of IBD is increasing in developing countries and declining in developed countries, affecting people of all ages.
View Article and Find Full Text PDFTL1A: A model for a precision medicine approach in the treatment of Crohn's disease and ulcerative colitis.
Adv Pharmacol
November 2024
F. Widjaja Inflammatory Bowel Disease Institute, Los Angeles, CA, United States.
Inflammatory bowel disease (IBD) is a collective term for chronic inflammatory diseases of the intestinal tract. The term IBD encompasses two main forms, Crohn's disease (CD) and Ulcerative colitis (UC). CD is characterized by inflammation throughout the length of the gut, especially the ileum and colon, and is often complicated with fistulae and/or intestinal strictures.
View Article and Find Full Text PDFPhase 2 Trial of Anti-TL1A Monoclonal Antibody Tulisokibart for Ulcerative Colitis.
N Engl J Med
September 2024
From the Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York (B.E.S.); the Departments of Medicine, Epidemiology, and Biostatistics, Western University, London, ON (B.G.F.), and the Division of Gastroenterology and Hepatology, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB (C.M.) - both in Canada; the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan (S.D.); the University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago (D.T.R.); Prometheus Biosciences, a subsidiary of Merck, Rahway, NJ (O.L., A.L., D.D.N., J. Lu, M.Y.); the Department of Gastroenterology, Melita Medical (J. Leszczyszyn), and the Department of Gastroenterology and Hepatology, Wroclaw Medical University (R.K.) - both in Wroclaw, Poland; F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles (D.P.B.M., S.T.); and GI Alliance, Southlake, TX (T.E.R.).
Background: Tulisokibart is a tumor necrosis factor-like cytokine 1A (TL1A) monoclonal antibody in development for the treatment of moderately to severely active ulcerative colitis. A genetic-based diagnostic test was designed to identify patients with an increased likelihood of response.
Methods: We randomly assigned patients with glucocorticoid dependence or failure of conventional or advanced therapies for ulcerative colitis to receive intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10) or placebo.
Targeting TNFRSF25 by agonistic antibodies and multimeric TL1A proteins co-stimulated CD8 T cells and inhibited tumor growth.
J Immunother Cancer
August 2024
National Institute of Biological Sciences, Beijing, China
Background: Tumor necrosis factor receptor superfamily 25 (TNFRSF25) is a T-cell co-stimulatory receptor. Expression of its ligand, TNF-like cytokine 1A (TL1A), on mouse tumor cells has been shown to promote tumor regression. This study aimed to develop TNFRSF25 agonists (both antibodies (Abs) and TL1A proteins) and to investigate their potential antitumor effects.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!