REVIEW article
Front. Immunol.
Sec. Mucosal Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1657071
This article is part of the Research TopicInnovations in targeting intestinal immunity for chronic inflammatory disordersView all 4 articles
TNFSF14 (LIGHT) in Intestinal Inflammation: Balancing Immune Activation and Resolution in IBD
Provisionally accepted
- 1Universita di Pavia, Pavia, Italy
- 2Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
- 3University of Cambridge, Cambridge, United Kingdom
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Inflammatory Bowel Disease (IBD), encompassing Crohn's disease and ulcerative colitis, is an umbrella term used to describe a group of autoimmune conditions characterized by chronic, relapsing inflammation of the gastrointestinal tract. The tumour necrosis factor superfamily member 14 (TNFSF14), also known as LIGHT, is a pleiotropic cytokine with diverse roles in immune regulation. Here, we review the multifaceted involvement of LIGHT in intestinal inflammation, particularly its dual capacity to both promote immune activation and facilitate inflammation resolution in the context of IBD. We explore the molecular mechanisms of LIGHT signalling through its receptors, Herpes Virus Entry Mediator (HVEM) and Lymphotoxin-β Receptor (LTβR), and how these distinct interactions dictate its pro-inflammatory or regulatory functions. Finally, we review the therapeutic potential of targeting this pathway, highlighting the results of recent clinical trials and exploring future strategies aimed at restoring immune homeostasis in patients with IBD.
Keywords: Light, TNFSF14, LTbR, lymphotoxin-β receptor, HVEM/TNFRSF14, DcR3 (TNFRSF6b), BTLA, B and T lymphocyte attenuator
Received: 30 Jun 2025; Accepted: 25 Aug 2025.
Copyright: © 2025 Mousa, Invernizzi, Jones and Mousa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hani S. Mousa, University of Cambridge, Cambridge, United Kingdom
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