Neuronal Control of Psoriatic Inflammation by Nonpeptidergic Nociceptors
Principal Investigator: Alejandra Mendoza, Ph.D.
Institution: The Scripps Research Institute - La Jolla
Grant Mechanism: Discovery Grant
Funding Amount: $75,000
Project Start Date: October 1, 2026
Project End Date: September 30, 2028
Status: Active
Keywords: Psoriasis, Animal models, Cell signaling, Inflammation, Neuroimmunology
Project Summary:
Psoriasis is a chronic inflammatory skin disease that affects millions of people worldwide. It causes painful, itchy skin lesions and is associated with other serious health conditions, yet current treatments do not work for everyone and often require lifelong use. While psoriasis is traditionally viewed as a disease of the immune system, growing evidence suggests that sensory nerves in the skin also play a critical role in driving and regulating inflammation. This research will investigate how a specific population of sensory nerve cells that detect pain and itch influences the immune response during psoriasis. We will study how these nerves sense the earliest signals produced in inflamed skin and how they communicate with immune cells to either amplify or limit inflammation. Using advanced genetic tools, we will selectively control the activity of these nerve cells to determine how they shape the development and severity of psoriasis-like skin inflammation and identify the molecular pathways involved. By uncovering how the nervous and immune systems work together in psoriasis, this project aims to reveal entirely new ways to treat inflammatory skin disease. Rather than targeting immune cells alone, future therapies may be able to modulate the communication between nerves and the immune system to reduce inflammation, relieve symptoms such as pain and itch, and improve the lives of people living with psoriasis.
How will your project help improve the lives of the 125 million affected by psoriatic disease?
Most current psoriasis treatments target the immune system, while effective for many patients, they do not address a key question: why does psoriatic disease so often become chronic and recurring, rather than resolving? This project investigates the possibility that sensory neurons and immune cells in the skin engage in feed-forward, amplifying loops, in which neuronal signals drive inflammation, and inflammation in turn sensitizes neurons, creating a self-sustaining cycle that may underlie not just itch and pain, but the persistence of disease itself. Therefore, novel therapies that target sensory neuron signaling could offer new options for patients who do not respond to current treatments, and could also work synergistically alongside existing therapies to break the cycle earlier and more completely, helping prevent the flares and chronic progression that define the lived experience of psoriatic disease for so many patients.
Why is psoriatic disease research important to you, personally? What role will this award play in your research efforts or career development?
While psoriasis isn't often thought of as life-threatening, it is extremely debilitating. Patients not only deal with visible symptoms; they carry out their daily lives while managing chronic pain and itch, alongside the constant psychological stress of living with a disease that can flare unpredictably. That burden, which is easy to underestimate from the outside, is part of what drives me to pursue mechanisms that current treatments do not yet address.
This award plays a pivotal role at this stage of my career. As an early-stage investigator, generating strong preliminary data on a genuinely novel mechanistic angle, sensory neuron subtypes as active regulators of psoriatic inflammation, is essential for building a research program and competing for larger federal funding. NPF's support allows me to pursue a higher-risk, higher-reward direction that might otherwise be difficult to fund at this stage, and it directly strengthens my ability to establish an independent research program dedicated to understanding and ultimately improving treatment for psoriatic disease.
Researcher Profile:
Alejandra Mendoza is an Assistant Professor in the Department of Immunology and Microbiology at The Scripps Research Institute in La Jolla, California. Her laboratory studies the communication between sensory neurons and immune cells in barrier tissues, with a particular focus on how this crosstalk shapes inflammation and tissue repair in the skin. Dr. Mendoza's research combines mouse genetics, and viral tools, and single-cell genomics, to dissect how distinct populations of sensory neurons regulate psoriatic disease. Her work aims to identify new, neuroimmune-informed strategies for treating inflammatory skin conditions.