Why the OX-40/OX-40L Pathway Matters in Atopic Dermatitis—and What’s Next: A Q&A with Johann Gudjonsson, MD, PhD

Johann Gudjonsson, MD, PhD

Photo courtesy of the International Psoriasis Council

At the 2025 Revolutionizing Atopic Dermatitis (RAD) conference in Nashville, TN, Johann Gudjonsson, MD, PhD, delivered a presentation exploring the OX-40/OX-40L signaling pathway and its central role in the pathogenesis of atopic dermatitis. In this interview with Patient Care, Gudjonsson, the Arthur C Curtis professor of skin molecular immunology at the University of Michigan, expands on the genetic underpinnings of the OX-40 axis, its role in immune system activation, and why it is an increasingly important therapeutic target. He also discusses emerging treatment strategies, including combination approaches, and reflects on the unique value of RAD as a disease-specific meeting. Read the full conversation below.

Patient Care: To start off, could you explain the focus of your presentation at RAD 2025?

Johann Gudjonsson, MD, PhD: Sure. My presentation focused on the OX-40/OX-40 ligand (OX-40L) signaling axis and its role in the biology and immunology of atopic dermatitis. I discussed how this pathway functions as a co-stimulatory signal between dendritic cells and T cells, driving immune activation and downstream cytokine release. I also highlighted the genetic component—specifically, how certain variants in this axis can increase susceptibility to atopic dermatitis and promote inflammation.

Patient Care: How does the OX-40 pathway play a central role in the pathogenesis of atopic dermatitis?

Dr. Gudjonsson: One of the most compelling pieces of evidence is its genetic link to the disease. We’ve identified variants in the OX-40/OX-40L axis that likely increase pathway activity, predisposing individuals to atopic dermatitis. Beyond genetics, we see significantly elevated expression of both the ligand and receptor in atopic dermatitis lesions, and importantly, they’re located in the same regions of the skin—suggesting direct interaction. This axis mediates communication between antigen-presenting dendritic cells and T cells, making it a critical component of the immunologic circuitry driving disease pathogenesis.

Patient Care: You also touched on emerging therapies. Are there any you're particularly excited about?

Dr. Gudjonsson: There’s a lot happening in the atopic dermatitis space—it’s really taken off over the past decade. We now have multiple novel agents targeting a range of pathways. OX-40/OX-40L is one of them, but others include anti–IL-31 receptor antibodies, anti–IL-13 therapies, IL-4 receptor blockers, JAK inhibitors, and new topical agents. What’s especially exciting is the shift toward combination therapies—pairing known mechanisms into single treatments. These combination strategies are starting to be evaluated in early trials, and I believe they hold the potential to outperform current monotherapies.

Patient Care: What do you hope clinicians will take away from your presentation?

Dr. Gudjonsson: First, that we’ve made tremendous progress. Our understanding of the genetics and immunology of atopic dermatitis has expanded dramatically, which is driving innovation in treatment. But I also want to emphasize that there’s still a lot we don’t know. There are aspects of the disease that remain poorly understood, and we need continued research to close those gaps.

Patient Care: As an expert in the field, how valuable do you find a disease-specific meeting like RAD?

Dr. Gudjonsson: Meetings like RAD are incredibly valuable. When you attend a conference focused on a single disease, you get a much deeper dive into both clinical and molecular aspects. I found it especially helpful to explore intersections between atopic dermatitis and other conditions like allergies, as well as underrepresented topics like itch and pruritus. There’s also detailed discussion on the molecular mechanisms and how emerging therapies align with those pathways. You just don’t get that level of depth at broader dermatology or immunology meetings. RAD is focused, but it goes deep—and that’s what makes it unique.

For more RAD 2025 meeting coverage, please click here.