# Epidermal Nonpeptidergic Nerves Modulate Cutaneous Immunity

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $534,812

## Abstract

Abstract
The skin is a highly innervated organ and contains numerous sensory afferent neurons that
respond to a diverse array of stimuli including touch, pruritogens (inducing itch) and noxious
agents (inducing pain). There are also many skin-resident immune cells including dendritic cells
and mast cells that make direct contact with sensory neurons. It has very recently become
appreciated that cutaneous sensory neurons and skin-resident innate immune cells work
synergistically to initiate local inflammation and host defense. We have previously shown that
TRPV1+ neurons that sense pain are necessary and sufficient for cutaneous innate Type-17
inflammation and host defense against C. albicans. Thus, a neuron subset associated with
painful stimuli is necessary and sufficient to drive a Type-17 immune response which is the
optimal immune response against extracellular pathogens that can cause painful stimuli. We
now propose to test the immunologic potential of nonpeptidergic sensory neurons are that can
be divided based on single cell RNAseq into at least 3 subsets: NP1, NP2, and NP3. The
overall goal of this proposal is to understand the unique contribution of individual subsets of
nonpeptidergic sensory neurons to the modulation of skin immunity. Exploring this neuro-
immune interaction will better define the cellular circuits driving inflammation and allow for the
use of agonists/antagonists that target neuron subsets in order to modulate specific types of
cutaneous immune responses without global immunosuppression. Specifically, we hypothesize
that NP1 sensory nerves function to suppress mast cell activity. We further hypothesize that the
NP2 and NP3 subsets that communicate itch sensation in response to pruritogens also
participate in the development of Type-2 immune responses analogous to TRPV1+ neurons and
Type-17 immune responses. The potential to modulate Th2 and mast cell function makes these
pathways potential key for allergic disease pathogenesis.

## Key facts

- **NIH application ID:** 10216987
- **Project number:** 5R01AR077341-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Kathryn Marie Albers
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $534,812
- **Award type:** 5
- **Project period:** 2020-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216987

## Citation

> US National Institutes of Health, RePORTER application 10216987, Epidermal Nonpeptidergic Nerves Modulate Cutaneous Immunity (5R01AR077341-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10216987. Licensed CC0.

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