Therapeutic Potential of Tulisokibart and Anti-TL1A Therapy in Inflammatory Disorders: Current Insights and Future Directions

Solitano V, Estevinho MM, Ungaro F et al (2025) TL1A inhibition in inflammatory bowel disease: a pipeline review. BioDrugs 39:171–183. https://doi.org/10.1007/s40259-025-00706-4

Article  PubMed  Google Scholar 

Bamias G, Menghini P, Pizarro TT, Cominelli F (2025) Targeting TL1A and DR3: the new frontier of anti-cytokine therapy in IBD. Gut 74:652–668. https://doi.org/10.1136/gutjnl-2024-332504

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hassan-Zahraee M, Ye Z, Xi L et al (2022) Antitumor necrosis factor-like ligand 1A therapy targets tissue inflammation and fibrosis pathways and reduces gut pathobionts in ulcerative colitis. Inflamm Bowel Dis 28:434–446. https://doi.org/10.1093/ibd/izab193

Article  PubMed  PubMed Central  Google Scholar 

Xu W-D, Li R, Huang A-F (2022) Role of TL1A in inflammatory autoimmune diseases: a comprehensive review. Front Immunol 13:891328. https://doi.org/10.3389/fimmu.2022.891328

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vieujean S, Jairath V, Peyrin-Biroulet L et al (2025) Understanding the therapeutic toolkit for inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 22:371–394. https://doi.org/10.1038/s41575-024-01035-7

Article  PubMed  Google Scholar 

Takedatsu H, Michelsen KS, Wei B et al (2008) TL1A (TNFSF15) regulates the development of chronic colitis by modulating both T-helper 1 and T-helper 17 activation. Gastroenterology 135:552–567. https://doi.org/10.1053/j.gastro.2008.04.037

Article  CAS  PubMed  PubMed Central  Google Scholar 

Clarke AW, Poulton L, Shim D et al (2018) An anti-TL1A antibody for the treatment of asthma and inflammatory bowel disease. mAbs 10:664–677. https://doi.org/10.1080/19420862.2018.1440164

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sands BE, Feagan BG, Peyrin-Biroulet L et al (2024) Phase 2 trial of anti-TL1A monoclonal antibody Tulisokibart for ulcerative colitis. N Engl J Med 391:1119–1129. https://doi.org/10.1056/NEJMoa2314076

Article  CAS  PubMed  Google Scholar 

Feagan BG, Sands BE, Siegel CA et al (2025) Safety and efficacy of the anti-TL1A monoclonal antibody tulisokibart for Crohn’s disease: a phase 2a induction trial. Lancet Gastroenterol Hepatol 10:715–725. https://doi.org/10.1016/S2468-1253(25)00071-8

Article  CAS  PubMed  Google Scholar 

Bittner S, Ehrenschwender M (2017) Multifaceted death receptor 3 signaling—promoting survival and triggering death. FEBS Lett 591:2543–2555. https://doi.org/10.1002/1873-3468.12747

Article  CAS  PubMed  Google Scholar 

Hayden MS, Ghosh S (2014) Regulation of NF-κB by TNF family cytokines. Semin Immunol 26:253–266. https://doi.org/10.1016/j.smim.2014.05.004

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ranjan K, Pathak C (2024) Cellular dynamics of Fas-associated death domain in the regulation of cancer and inflammation. Int J Mol Sci 25:3228. https://doi.org/10.3390/ijms25063228

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lonsdale J, Thomas J, Salvatore M et al (2013) The Genotype-Tissue Expression (GTEx) project. Nat Genet 45:580–585. https://doi.org/10.1038/ng.2653

Article  CAS  Google Scholar 

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

Article  CAS  PubMed  PubMed Central  Google Scholar 

Luo Y, Guo J, Jia W et al (2021) TNF-like ligand 1 aberrance aggravates nonalcoholic steatohepatitis via M1 macrophage polarization. Oxid Med Cell Longev 2021:3877617. https://doi.org/10.1155/2021/3877617

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tian F, Grimaldo S, Fugita M et al (2007) The endothelial cell-produced antiangiogenic cytokine vascular endothelial growth inhibitor induces dendritic cell maturation. J Immunol 179:3742–3751. https://doi.org/10.4049/jimmunol.179.6.3742

Article  CAS  PubMed  Google Scholar 

Slebioda TJ, Bojarska-Junak A, Cyman M et al (2017) Expression of death receptor 3 on peripheral blood mononuclear cells differes in adult IBD patients and children with newly diagnosed IBD. Cytometry B Clin Cytom 92:165–169. https://doi.org/10.1002/cyto.b.21372

Article  CAS  PubMed  Google Scholar 

Han F, Song J, Jia W et al (2020) TL1A primed dendritic cells activation exacerbated chronic murine colitis. Life Sci 262:118220. https://doi.org/10.1016/j.lfs.2020.118220

Article  CAS  PubMed  Google Scholar 

Taraban VY, Slebioda TJ, Willoughby JE et al (2011) Sustained TL1A expression modulates effector and regulatory T-cell responses and drives intestinal goblet cell hyperplasia. Mucosal Immunol 4:186–196. https://doi.org/10.1038/mi.2010.70

Article  CAS  PubMed  Google Scholar 

Karlmark KR, Tacke F, Dunay IR (2012) Monocytes in health and disease - minireview. Eur J Microbiol Immunol 2:97–102. https://doi.org/10.1556/EuJMI.2.2012.2.1

Article  CAS  Google Scholar 

Sreejit G, Fleetwood AJ, Murphy AJ, Nagareddy PR (2020) Origins and diversity of macrophages in health and disease. Clin Transl Immunol 9:e1222. https://doi.org/10.1002/cti2.1222

Article  Google Scholar 

McLaren JE, Calder CJ, McSharry BP et al (2010) The TNF-like protein 1A–death receptor 3 pathway promotes macrophage foam cell formation in vitro. J Immunol 184:5827–5834. https://doi.org/10.4049/jimmunol.0903782

Article  CAS  PubMed  PubMed Central  Google Scholar 

Maixner N, Pecht T, Haim Y et al (2020) A TRAIL-TL1A Paracrine Network Involving Adipocytes, Macrophages, and Lymphocytes Induces Adipose Tissue Dysfunction Downstream of E2F1 in Human Obesity. Diabetes 69:2310–2323. https://doi.org/10.2337/db19-1231

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tettoni E, Gabbiadini R, Dal Buono A et al (2025) TL1A as a Target in Inflammatory Bowel Disease: Exploring Mechanisms and Therapeutic Potential. Int J Mol Sci 26:5017. https://doi.org/10.3390/ijms26115017

Article  CAS  PubMed  PubMed Central  Google Scholar 

Richard AC, Ferdinand JR, Meylan F et al (2015) The TNF-family cytokine TL1A: from lymphocyte costimulator to disease co-conspirator. J Leukoc Biol 98:333–345. https://doi.org/10.1189/jlb.3RI0315-095R

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yu X, Pappu R, Ramirez-Carrozzi V et al (2014) TNF superfamily member TL1A elicits type 2 innate lymphoid cells at mucosal barriers. Mucosal Immunol 7:730–740. https://doi.org/10.1038/mi.2013.92

Article  CAS  PubMed  Google Scholar 

Machida K, Aw M, Salter BMA et al (2020) The role of the TL1A/DR3 axis in the activation of group 2 innate lymphoid cells in subjects with eosinophilic asthma. Am J Respir Crit Care Med 202:1105–1114. https://doi.org/10.1164/rccm.201909-1722OC

Article  CAS  PubMed  Google Scholar 

Castellanos JG, Woo V, Viladomiu M et al (2018) Microbiota-Induced TNF-like Ligand 1A Drives Group 3 Innate Lymphoid Cell-Mediated Barrier Protection and Intestinal T Cell Activation during Colitis. Immunity 49:1077–1089e5. https://doi.org/10.1016/j.immuni.2018.10.014

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