# Neuronal and molecular mechanisms underlying neural regulation of innate immunity

> **NIH NIH R35** · WASHINGTON STATE UNIVERSITY · 2020 · $382,500

## Abstract

Project Summary
Insufficient or excessive immune responses to pathogen infection are major causes of disease. Increasing
evidence indicates that the nervous system regulates the immune system to help maintain immunological
homeostasis. However, the precise mechanisms of this regulation are largely unknown. While many aspects
of neural regulation of immunity are difficult to dissect in complex mammalian systems, the nematode
Caenorhabditis elegans is an excellent model organism for such studies due to its simple, well-defined nervous
system and an immune system that resembles the human innate immune system in several key respects. By
using C. elegans, we demonstrated that neurotransmitter octopamine released from two interneurons
designated as RIC binds to a G protein-coupled receptor OCTR-1, which, in turn, functions in the sensory ASH
neurons to suppress innate immune response in non-neural tissues. We propose to dissect the neuronal and
molecular mechanisms of this octopaminergic immuno-inhibitory pathway. We will determine where the
immuno-modulatory signals originate in the OCTR-1 neural circuit, how the signals are relayed from the circuit
to the non-neural tissues, what molecules in the non-neural tissues mediate innate immune responses, and
how octopamine level is regulated in C. elegans in response to pathogen infection.  The successful completion
of this work will provide significant new data necessary to understand the neuronal and molecular mechanisms
underlying neural control of innate immunity in mammals. As excessive innate immune responses have been
linked to human health conditions such as Crohn's disease, rheumatoid arthritis, atherosclerosis, diabetes and
Alzheimer's disease, the octopaminergic immuno-inhibitory pathway can be exploited to therapeutic
advantage.

## Key facts

- **NIH application ID:** 10001070
- **Project number:** 5R35GM124678-04
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Jingru Sun
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,500
- **Award type:** 5
- **Project period:** 2017-09-12 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001070

## Citation

> US National Institutes of Health, RePORTER application 10001070, Neuronal and molecular mechanisms underlying neural regulation of innate immunity (5R35GM124678-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001070. Licensed CC0.

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