TL1A Inhibition in Inflammatory Bowel Disease: A Pipeline Review

Fudman D, McConnell RA, Ha C, Singh S. Modern advanced therapies for inflammatory bowel diseases: practical considerations and positioning. Clin Gastroenterol Hepatol. 2024. https://doi.org/10.1016/j.cgh.2024.06.050.

Article  PubMed  Google Scholar 

Solitano V, Dal Buono A, Gabbiadini R, Wozny M, Repici A, Spinelli A, et al. Fibro-stenosing Crohn’s disease: what is new and what is next? J Clin Med. 2023. https://doi.org/10.3390/jcm12093052.

Article  PubMed  PubMed Central  Google Scholar 

Gordon IO, Agrawal N, Willis E, Goldblum JR, Lopez R, Allende D, et al. Fibrosis in ulcerative colitis is directly linked to severity and chronicity of mucosal inflammation. Aliment Pharmacol Ther. 2018;47(7):922–39. https://doi.org/10.1111/apt.14526.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bamias G, Pizarro TT, Cominelli F. Immunological regulation of intestinal fibrosis in inflammatory bowel disease. Inflamm Bowel Dis. 2022;28(3):337–49. https://doi.org/10.1093/ibd/izab251.

Article  PubMed  Google Scholar 

Cordero RY, Cordero JB, Stiemke AB, Datta LW, Buyske S, Kugathasan S, et al. Trans-ancestry, Bayesian meta-analysis discovers 20 novel risk loci for inflammatory bowel disease in an African American, East Asian and European cohort. Hum Mol Genet. 2023;32(5):873–82. https://doi.org/10.1093/hmg/ddac269.

Article  CAS  PubMed  Google Scholar 

Yamazaki K, McGovern D, Ragoussis J, Paolucci M, Butler H, Jewell D, et al. Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn’s disease. Hum Mol Genet. 2005;14(22):3499–506. https://doi.org/10.1093/hmg/ddi379.

Article  CAS  PubMed  Google Scholar 

Yang DH, Yang SK, Song K, Hong M, Park SH, Lee HS, et al. TNFSF15 is an independent predictor for the development of Crohn’s disease-related complications in Koreans. J Crohns Colitis. 2014;8(10):1315–26. https://doi.org/10.1016/j.crohns.2014.04.002.

Article  PubMed  Google Scholar 

Valatas V, Kolios G, Bamias G. TL1A (TNFSF15) and DR3 (TNFRSF25): a co-stimulatory system of cytokines with diverse functions in gut mucosal immunity. Front Immunol. 2019;10:583. https://doi.org/10.3389/fimmu.2019.00583.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Solitano V, Jairath V, Ungaro F, Peyrin-Biroulet L, Danese S. TL1A inhibition for inflammatory bowel disease treatment: from inflammation to fibrosis. Medicine. 2024;5(5):386–400. https://doi.org/10.1016/j.medj.2024.03.010.

Article  CAS  Google Scholar 

Bamias G, Menghini P, Pizarro TT, Cominelli F. Targeting TL1A and DR3: the new frontier of anti-cytokine therapy in IBD. Gut. 2024. https://doi.org/10.1136/gutjnl-2024-332504.

Article  Google Scholar 

Banfield C, Rudin D, Bhattacharya I, Goteti K, Li G, Hassan-Zahraee M, et al. First-in-human, randomized dose-escalation study of the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of PF-06480605 in healthy subjects. Br J Clin Pharmacol. 2020;86(4):812–24. https://doi.org/10.1111/bcp.14187.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Danese S, Klopocka M, Scherl EJ, Romatowski J, Allegretti JR, Peeva E, et al. Anti-TL1A antibody PF-06480605 safety and efficacy for ulcerative colitis: a phase 2a single-arm study. Clin Gastroenterol Hepatol. 2021;19(11):2324-32.e6. https://doi.org/10.1016/j.cgh.2021.06.011.

Article  CAS  PubMed  Google Scholar 

Yi Z, Wallis AM, Bishop GA. Roles of TRAF3 in T cells: many surprises. Cell Cycle. 2015;14(8):1156–63. https://doi.org/10.1080/15384101.2015.1021524.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Migone T-S, Zhang J, Luo X, Zhuang L, Chen C, Hu B, et al. TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator. Immunity. 2002;16(3):479–92.

Article  CAS  PubMed  Google Scholar 

Zhan C, Yan Q, Patskovsky Y, Li Z, Toro R, Meyer A, et al. Biochemical and structural characterization of the human TL1A ectodomain. Biochemistry. 2009;48(32):7636–45. https://doi.org/10.1021/bi900031w.

Article  CAS  PubMed  Google Scholar 

Schreiber TH, Podack ER. Immunobiology of TNFSF15 and TNFRSF25. Immunol Res. 2013;57(1–3):3–11. https://doi.org/10.1007/s12026-013-8465-0.

Article  CAS  PubMed  Google Scholar 

Fang L, Adkins B, Deyev V, Podack ER. Essential role of TNF receptor superfamily 25 (TNFRSF25) in the development of allergic lung inflammation. J Exp Med. 2008;205(5):1037–48. https://doi.org/10.1084/jem.20072528.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Meylan F, Richard AC, Siegel RM. TL1A and DR3, a TNF family ligand-receptor pair that promotes lymphocyte costimulation, mucosal hyperplasia, and autoimmune inflammation. Immunol Rev. 2011;244(1):188–96. https://doi.org/10.1111/j.1600-065X.2011.01068.x.

Article  CAS  PubMed  Google Scholar 

Wen L, Zhuang L, Luo X, Wei P. TL1A-induced NF-kappaB activation and c-IAP2 production prevent DR3-mediated apoptosis in TF-1 cells. J Biol Chem. 2003;278(40):39251–8. https://doi.org/10.1074/jbc.M305833200.

Article  CAS  PubMed  Google Scholar 

Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell. 2003;114(2):181–90. https://doi.org/10.1016/s0092-8674(03)00521-x.

Article  CAS  PubMed  Google Scholar 

Wang D, Li H, Duan YY, Han F, Luo YX, Wu MY, et al. TL1A modulates the severity of colitis by promoting Th9 differentiation and IL-9 secretion. Life Sci. 2019;231: 116536. https://doi.org/10.1016/j.lfs.2019.06.011.

Article  CAS  PubMed  Google Scholar 

Meng F, Jiang X, Wang X, Zheng Q, Wang XN, Mei C, et al. Tumor necrosis factor-like cytokine 1A plays a role in inflammatory bowel disease pathogenesis. Proc Natl Acad Sci USA. 2023;120(34): e2120771120. https://doi.org/10.1073/pnas.2120771120.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Takedatsu H, Michelsen KS, Wei B, Landers CJ, Thomas LS, Dhall D, et al. TL1A (TNFSF15) regulates the development of chronic colitis by modulating both T-helper 1 and T-helper 17 activation. Gastroenterology. 2008;135(2):552–67. https://doi.org/10.1053/j.gastro.2008.04.037.

Article  CAS  PubMed  Google Scholar 

Castellanos JG, Woo V, Viladomiu M, Putzel G, Lima S, Diehl GE, et al. Microbiota-induced TNF-like ligand 1A drives group 3 innate lymphoid cell-mediated barrier protection and intestinal T cell activation during colitis. Immunity. 2018;49(6):1077-89.e5. https://doi.org/10.1016/j.immuni.2018.10.014.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sidhu-Varma M, Shih DQ, Targan SR. Differential levels of Tl1a affect the expansion and function of regulatory T cells in modulating murine colitis. Inflamm Bowel Dis. 2016;22(3):548–59. https://doi.org/10.1097/mib.0000000000000653.

Article  PubMed  Google Scholar 

Pai YC, Weng LT, Wei SC, Wu LL, Shih DQ, Targan SR, et al. Gut microbial transcytosis induced by tumor necrosis factor-like 1A-dependent activation of a myosin light chain kinase splice variant contributes to IBD. J Crohns Colitis. 2020;15(2):258–72. https://doi.org/10.1093/ecco-jcc/jjaa165.

Article  PubMed  PubMed Central  Google Scholar 

Prehn JL, Mehdizadeh S, Landers CJ, Luo X, Cha SC, Wei P, et al. Potential role for TL1A, the new TNF-family member and potent costimulator of IFN-gamma, in mucosal inflammation. Clin Immunol. 2004;112(1):66–77. https://doi.org/10.1016/j.clim.2004.02.007.

Article  CAS  PubMed  Google Scholar 

Bamias G, Martin C 3rd, Marini M, Hoang S, Mishina M, Ross WG, et al. Expression, localization, and functional activity of TL1A, a novel Th1-polarizing cytokine in inflammatory bowel disease. J Immunol. 2003;171(9):4868–74.

Comments (0)

No login
gif