In vitro modeling of human autonomic dysfunctions: focus on neuroimmune interactions

• Grant number: 24/23316-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2025
• End date: February 28, 2029
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Pedro Lourenço Katayama
• Grantee: Luana Salmeron Lopes
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 23/07741-8 - Exploring the mechanisms and consequences of autonomic dysfunction in autoimmune diseases: an integrative approach, AP.JP

Abstract

Numerous studies have shown that norepinephrine modulates macrophage activity via alpha- and beta-adrenergic receptors across various contexts. However, due to technological and experimental limitations, these findings have been largely indirect, relying on exogenous substances (such as norepinephrine and adrenergic receptor blockers or activators) as proof of concept. In recent years, human induced pluripotent stem cells (hiPSCs) have gained popularity for reliably generating different types of human cells, including sympathetic neurons and macrophages. In this project, we aim to utilize hiPSC-derived sympathetic neurons and macrophages to develop and characterize new in vitro models that will facilitate the study of neuroimmune interactions under both physiological and pathophysiological conditions. Our proposed model will enable us to explore the effects of endogenous norepinephrine, synthesized and secreted by hiPSC-derived sympathetic neurons, on the phenotype and function of human macrophages. Additionally, we will examine the impact of secreted products from various types of human macrophages on the excitability of hiPSC-derived sympathetic neurons. This innovative model represents a groundbreaking approach to studying neuroimmune interactions, and the mechanisms we uncover will yield novel results with significant scientific relevance and considerable translational potential.