NPF-Funded Research

Project Summary:

Intense itching sensed by discrete subsets of neurons or pruriceptors is one of the most frequent symptoms in psoriatic patients. However, how specific pruriceptors contribute to the pathogenesis of psoriasis is undefined. Pruriceptors bearing the receptor MrgprD were recently recognized to restrain cutaneous inflammation, yet whether these molecularly distinct nerve afferents can be targeted for stable immunomodulation and treatment of psoriasis is unknown. This proposal will determine how skin inflammatory mediators released in psoriatic patients affect the functions of MrgprD+ neurons and the therapeutic potential of stimulating MrgprD+ afferents to ameliorate psoriatic disease by reshaping the cytokine profile of skin lymphocytes.

How will your project help improve the lives of the 125 million affected by psoriatic disease?

Current therapies for psoriasis suppress the aberrant action and secretion of IL-17 and other cytokines to improve the quality of life of psoriatic patients. However, long-term adherence to these therapies poses heavy economic and logistical burdens, and chronic use of immunosuppressive agents can lead to increased risk of infections and aggravated or new paradoxical psoriasis. We propose that stable immunomodulation to ameliorate psoriasiform inflammation can be achieved by targeting MrgprD+ afferents that reshape the cytokine profile of skin T cells. Understanding how dysregulated MrgprD+ neurons in psoriasis can be reactivated may lead to life-changing therapies that stably control cytokine responses and psoriatic disease.

Why is psoriatic disease research important to you, personally? What role will this award play in your research efforts or career development?

My long-term goal is to define how neurons, immune cells, and keratinocytes collectively regulate host-protective skin immunity. My postdoctoral studies, supported by the prestigious NIH-NIAID K99/R00 Pathway to Independence award, revealed that MrgprA3+ neurons confer cutaneous protection against parasitic helminths. The NPF Early Career Research Grant will support my second research direction to investigate how molecularly distinct MrgprD+ afferents reshape the cytokine profile of skin T cells and ameliorate psoriatic inflammation by inducing the anti-inflammatory cytokine IL-10. This proposal will define the therapeutic potential of targeting MrgprD+ neurons for stable immunomodulation and treatment of psoriasis.

Researcher Profile:

Dr. Inclan-Rico’s lifelong interest in neuromodulation of host immunity started after majoring in biochemistry and pharmaceutics at the School of Chemistry of the National Autonomous University of Mexico (UNAM) and pursuing a doctorate in biomedical sciences at Rutgers, The State University of New Jersey. There, he joined the laboratory of Dr. Mark Siracusa and led two projects that investigated how tissue immunity against parasitic helminths is developed, which may inform the development of new therapies for chronic immunopathologies. As a graduate student, Dr. Inclan-Rico's studies discovered that the neuropeptide Neuromedin B (NMB) prevents excessive tissue remodeling by limiting cytokine secretion in group 2 innate lymphoid cells. This study highlighted how peripheral neurons regulate tissue immunity, which encouraged him to continue his postdoctoral training co-mentored by Drs. De’Broski Herbert and Wenqin Luo at the University of Pennsylvania, where his work defined how parasites inactivate itch-inducing neurons that elicit IL-17-mediated cutaneous anti-helminth immunity. In a subsequent study, they also showed that pain-sensing neurons are inhibited by parasites to promote parasite dissemination. These exciting findings have received prestigious awards from the Life Sciences Research Foundation (LSRF) and an NIH-NIAID K99/R00 Pathway to Independence award, which have paved the way to start his laboratory as an Assistant Professor at Virginia Commonwealth University. His research program will define the contributions of itch-inducing neurons to skin inflammation during infectious and inflammatory conditions, including psoriasis.