# Immune Functions of Cutaneous Nociceptors

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $332,262

## Abstract

Abstract
The skin is a highly innervated organ and contains numerous sensory afferent nerve fibers that respond to a
diverse array of stimuli ranging from gentle touch to noxious, painful stimuli. There are also many skin-resident
immune cells including several subsets of dendritic cells that direct effector responses from skin-resident
innate and adaptive T cells. During C. albicans skin infection, cutaneous nociceptors (unmyelinated pain-
sensing neurons) are able to directly sense C. albicans and are required for the resulting cascade of down-
stream Type 17 immune events resulting in efficient clearance of C. albicans. In addition, in models of
psoriasis-like skin inflammation, nociceptors are required for cutaneous Type 17 inflammation. A key step in
this cascade is the interaction of nociceptors with cutaneous dendritic cells that drive both innate Type 17
inflammation and are required for the development of adaptive Th17 cells that provide long-term protection.
This could explain why in human patients, loss of nerve innervation or spinal cord injury results in clearance of
psoriatic lesions in denervated limbs as well as increased rates of superficial C. albicans infection. Thus, in
both humans and mice, cutaneous nerves play a critical role in regulating the Type 17 immunity in the skin
during both infection and autoimmunity.
Despite this progress, a large number of important unanswered questions remain on how the nervous and
immune systems communicate in response to immune challenges. The goal of this project is to define the
mechanism(s) of neuronal activation and resulting neuronal influence on immune responses in the setting of
host defense and autoimmunity. In particular, we will test how nociceptors are activated and the effect of
isolated nociceptor activation. By dissecting these pathways in detail we expect to create a rational use for
novel pharmacological agents that target peripheral nerve function in the treatment of skin diseases.
We hypothesize that the nociceptive subset of cutaneous afferents identified by expression of TRPV1 directly
recognize C. albicans and Imiquimod through engagement of the TLR pathway. We will test this hypothesis by
comparing responses of dorsal root ganglion neurons isolated from mice with genetic defects in the TLR
pathway to mutant strains of C. albicans in vitro. We will also determine whether activation of nociceptors in
vivo is sufficient for the establishment of Type 17 immunity using optogenetics. Finally, using mice with genetic
ablation of nociceptors, we will test whether nociception is required for the development of adaptive Th17 cells
in vivo.

## Key facts

- **NIH application ID:** 9844929
- **Project number:** 5R01AR071720-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Kathryn Marie Albers
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $332,262
- **Award type:** 5
- **Project period:** 2017-03-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9844929

## Citation

> US National Institutes of Health, RePORTER application 9844929, Immune Functions of Cutaneous Nociceptors (5R01AR071720-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9844929. Licensed CC0.

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