Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Sep 18;191(4):488-496.
doi: 10.1093/bjd/ljae230.

The role of OX40 ligand/OX40 axis signalling in atopic dermatitis

Emma Guttman-Yassky  1 , Michael Croft  2 , Bob Geng  3 , Natalie Rynkiewicz  4 , Davide Lucchesi  4 , Mark Peakman  4 , Cassandra van Krinks  4 , Wendell Valdecantos  5 , Heming Xing  4 , Stephan Weidinger  6
Affiliations
Review

The role of OX40 ligand/OX40 axis signalling in atopic dermatitis

Emma Guttman-Yassky et al. Br J Dermatol. .

Abstract

Atopic dermatitis (AD) is a heterogeneous inflammatory condition involving multiple immune pathways mediated by pathogenic T cells. OX40 ligand (OX40L) and OX40 are costimulatory immune checkpoint molecules that regulate effector and memory T-cell activity and promote sustained immune responses in multiple immunological pathways, including T helper (Th)2, Th1, Th17 and Th22. As such, OX40L/OX40 signalling between antigen-presenting cells (APCs) and activated T cells postantigen recognition promotes pathogenic T-cell proliferation and survival. Under inflammatory conditions, OX40L is upregulated on APCs, enhancing the magnitude of antigen-specific T-cell responses and secretion of proinflammatory cytokines. In AD, OX40L/OX40 signalling contributes to the amplification and chronic persistence of T-cell-mediated inflammation. Recent therapeutic success in clinical trials has highlighted the importance of the OX40L/OX40 axis as a promising target for the treatment of AD. Here, we discuss the many factors that are involved in the expression of OX40L and OX40, including the cytokine milieu, antigen presentation, the inflammatory environment in AD, and the therapeutic direction influenced by this costimulatory pathway.

Plain language summary

Atopic dermatitis (AD) (also known as atopic eczema) is a common skin disease caused by inflammation, and affects 2–3 of every 10 people worldwide. AD affects people of all ages and can cause a range of symptoms, including dry thickened skin, itchiness, rashes and pain. Despite the recent addition of new targeted treatment options, there is still a need for new treatments for people with moderate-to-severe AD. New drugs are being studied that target two important signalling molecules in the immune system, called OX40 ligand (OX40L) and OX40. OX40L and OX40 bind together to continue the cycle of immune system activation, leading to increasing symptoms of AD. Blocking the OX40L and OX40 interaction may ease or stop symptoms of AD. This review outlines what is currently known about the causes of AD, including the role played by the immune system and specifically the role of OX40L and OX40. We also highlight the development of new treatments that target the OX40L and OX40 interaction to treat AD, and suggest what the future may hold for managing AD.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest E.G.-Y. is an employee of Mount Sinai and has received research grants from LEO Pharma, Pfizer, Amgen, GSK, Incyte, Sanofi, Bristol Myers Squibb, Aslan, Regeneron, AnaptysBio, Concert, Janssen, Q32Bio, AbbVie, Eli Lilly, Arcutis and Inmagene Bio, and consulted for AbbVie, Almirall, Amgen, AnaptysBio, Apogee Therapeutics, Apollo Therapeutics Limited, Artax Biopharma Inc., AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Cara Therapeutics, Centrexion Therapeutics Corporation, Connect Biopharm, Eli Lilly, Enveda Biosciences, Escient Pharmaceuticals, Inc., Fairmount Funds Management LLC, FL2022-001, Inc., Galderma, Gate Bio, Google Ventures (GV), GSK Immunology, Inc., Incyte, Inmagene, Janssen Biotech, Japan Tobacco, Jasper Therapeutics, Kyowa Kirin, Kymera Therapeutics, Inc., LEO Pharma, Merck, Nektar Therapeutics, Novartis Pharmaceuticals Corporation, NUMAB Therapeutics AG, OrbiMed Advisors LLC, Otsuka, Pfizer, Pharmaxis Ltd, Pioneering Medicine VII, Inc., Proteologix US Inc, RAPT, RayThera, Inc, Regeneron Pharmaceuticals, Ribon Therapeutics, Inc., Sanofi, SATO, Schrödinger, Inc., Sun Pharma Advanced Research Company (SPARC), Teva Branded Pharmaceutical Products R&D, Inc. and UCB. M.C. has received consulting fees or speaking honoraria from Sanofi, Amgen, UCB, MedImmune, Millennium, Perseid, Celgene, Novo Nordisk, Merck, AbbVie, Tanabe, Zai Lab, Merrimack, Pfizer, AnaptysBio, Celsius Therapeutics, HifiBio, Kiniksa, Shattuck Labs, Prometheus Biosciences, Invectys, Virtici, Capella Bioscience and RAPT Therapeutics, and research funds from Kyowa Kirin, Bristol Myers Squibb, Janssen, and Eli Lilly. He has licensed patents on OX40 and OX40L. B.G. has received consulting fees or speaking honoraria from Sanofi, Regeneron, Pfizer, AbbVie, LEO Pharma, Eli Lilly, Novartis and Incyte, and research funds from Sanofi, Regeneron, LEO Pharma, Eli Lilly, Novartis, Incyte and Amgen. N.R., D.L., M.P., C.v.K., W.V. and H.X. are employees of Sanofi and may hold stock and/or stock options in the company. S.W. has received institutional research grants from LEO Pharma, Pfizer inc. and Sanofi, and has performed consulting work and lectures for AbbVie, Almirall, Boehringer, Eli Lilly, Galderma, GSK, Kymab, LEO Pharma, Pfizer, Sanofi and Regeneron.

MeSH terms

Grants and funding