Leveraging Human Skin Dendritic Cells to Unravel Immune Mechanisms and Advance Therapies for Psoriasis
Principal Investigator: Eynav Klechevsky, Ph.D.
Institution: Washington University in St. Louis
Grant Mechanism: R01 Bridge Grant
Funding Amount: $100,000
Project Start Date: August 1, 2025
Project End Date: July 31, 2026
Status: Active
Keywords: Psoriasis, Basic Science, Clinical Research, Biologics, Inflammation, Immunology, Multi-omics, Disease Models
Project Summary:
Our Project directly advances the path toward a cure for psoriasis by targeting a novel, disease-driving immune cell subset—CD5+ dendritic cells (DCs). Unlike current treatments that broadly suppress inflammation, our approach focuses on rewiring the immune system at its source. By defining the molecular mechanisms that govern CD5+ DC development and function, and their role in shaping inflammatory T cell responses, we aim to uncover precise intervention points that can halt or reverse disease progression. Furthermore, by linking CD5+ DC activity to therapeutic outcomes and identifying treatment-responsive immune pathways, we anticipate discovering mechanistic targets that can inform future precision therapies.
How will your project help improve the lives of the 125 million affected by psoriatic disease?
Despite advances in psoriasis treatments, approximately half of the 125 million people affected worldwide do not achieve sustained relief. A key reason is that current therapies primarily target broad immune pathways or symptoms, often leaving underlying triggers of inflammation untouched. Our approach is fundamentally different: rather than targeting the “usual suspects” in psoriasis therapy, we focus on a novel, previously underexplored immune cell subset. Dendritic cells sit at the very beginning of the inflammatory cascade, specifically activating the immune system in psoriatic skin lesions. Ultimately, we aim to offer hope to patients who have failed multiple therapies by identifying a new and distinct biological route for treatment.
Why is psoriatic disease research important to you, personally? What role will this award play in your research efforts or career development?
As an immunologist, I’ve long been driven by a desire to understand why the immune system turns against the body in diseases like psoriasis. Psoriasis is a visible and distressing manifestation of immune imbalance, where the immune system becomes chronically overactive and mistakenly targets the skin. Understanding the mechanisms behind this disease provides valuable insights into how the immune system can malfunction—and how we might bring it back into balance.
Personally, I find this research deeply motivating because it holds the potential to transform how we treat not only psoriasis but also other major conditions driven by immune dysregulation. By focusing on a specific population of dendritic cells, which are enriched in psoriatic lesions, we’re investigating an immune cell subset at the crossroads of inflammation and tolerance.
Insights from this work may allow us to:
- Reverse or prevent psoriatic inflammation by selectively targeting the earliest immune triggers of disease.
- Refine cancer immunotherapies, where overstimulation of the immune system can cause toxic side effects, such as inflammatory skin reactions.
- Develop better skin-delivered vaccines by understanding how to optimize dendritic cell function in the skin.
Psoriatic disease research is therefore not isolated—it informs broader areas of medicine, including cancer and autoimmunity. The opportunity to translate these discoveries into novel treatments that are both safe and effective fuels my scientific passion and is a driving force in my career.
Researcher Profile:
Eynav Klechevsky, Ph.D., is an Associate Professor of Pathology & Immunology at Washington University School of Medicine in St. Louis. Her laboratory focuses on dendritic cells and their role in immune regulation and disease, particularly in cancer and inflammatory disorders like psoriasis. Dr. Klechevsky has published widely in top journals and has pioneered approaches to harness dendritic cells for immunotherapy. Her work bridges fundamental immunology with clinical application.