“Listen to your nerves”: Itch-inducing neurons distinctly modulate skin immunity

Juan Inclan-Rico, PhD
Postdoctoral Researcher
University of Pennsylvania, School of Veterinary Medicine 
Philadelphia, PA, USA

This conference is hosted by Hideto Takahashi, MD, PhD. This conference is part of the the IRCM Early-Career Scientist Seminar Series (ECS³), a groundbreaking initiative whose mission is to showcase early career scientists. This is a great opportunity to discover the exciting projects of these researchers in training in front of a multidisciplinary audience.

About the conference
Skin employs interdependent cellular networks for barrier integrity and host immunity, but most underlying mechanisms remain obscure. In contrast to painful or itchy reactions caused by bacteria or fungi, skin exposure to the blood fluke Schistosoma mansoni often goes unnoticed and causes mild dermatitis that results in chronic systemic infections. The successful parasitism exhibited by S. mansoni is attributed to its remarkable capacity to modulate tissue immunity, but whether this regulation extends to other cells is unknown. Dr. Inclan-Rico’s postdoctoral work (Inclan-Rico et al. Nature Immunology, 2024 & The Journal of Immunology, 2025)  demonstrates that S. mansoni inactivates subsets of itch- and pain-inducing neurons that elicit cutaneous anti-helminth immunity by promoting cytokine secretion from cutaneous myeloid cells. Surprisingly, his studies also show that molecularly distinct polymodal nerve afferents possess anti-inflammatory properties to ameliorate psoriatic inflammation during psoriasis. These studies constitute the foundation of his independent research program to investigate how itch-inducing neurons regulate skin inflammation during infectious and non-infectious conditions, supported by the NIH-NIAID K99/R00 Pathway to Independence Award and the Life Sciences Research Foundation Fellowship.

About the speaker
Dr. Inclan-Rico’s long-term goal is to define the neuro-immune interactions that regulate host-protective immunity at barrier tissues. His 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 spending a year in the laboratory of Dr. Luis Ulloa at Rutgers University studying how the vagus nerve and dopamine can inhibit systemic inflammation and improve survival in sepsis. This experience motivated him to pursue a doctorate in biomedical sciences at Rutgers, where he joined the laboratory of Dr. Mark Siracusa and led two projects that investigated how tissue immunity against parasitic helminths is developed. Parasitic helminths have evolved alongside their mammalian hosts for millennia, in part, due to their remarkable capacity to regulate tissue immunity and establish chronic infections in barrier sites. Understanding the regulation of host immunity by helminths may inform the development of new therapies for chronic immunopathologies. As a graduate student, Dr. Inclan-Rico defined a novel function of basophils that prevents excessive tissue remodeling after helminth-induced lung injury. Basophils promote the expression of the receptor for the neuropeptide Neuromedin B (NMB) in group 2 innate lymphoid cells, which in turn limits their cytokine secretion. This study highlighted how peripheral neurons regulate tissue immunity, which encouraged him to continue his postdoctoral training in the laboratory of Dr. De’Broski Herbert at the University of Pennsylvania, where his work defined how the blood fluke Schistosoma mansoni inactivates itch-inducing neurons bearing the receptor MrgprA3 that elicit IL-17-mediated cutaneous anti-helminth immunity by inducing pro-inflammatory cytokine secretion in myeloid cells. In a subsequent study, they also showed that pain-sensing TRPV1 neurons are inhibited by S. mansoni 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 for his research program that will define the contributions of itch-inducing neurons to skin inflammation during infectious and non-infectious conditions, including psoriasis.