# Integrin receptor: A connecting link between skin and peripheral sensing neurons in atopic dermatitis

> **NIH NIH R01** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2022 · $212,636

## Abstract

Project Summary
Atopic dermatitis is an inflammatory skin condition that affects an estimated 30% of the US population, mostly
children and adolescents. Atopic dermatitis is characterized by chronically itchy skin that can weep clear fluid
when scratched, and patients with atopic dermatitis are susceptible to bacterial, viral and fungal skin infection.
There currently are no effective treatments for the chronic itch other than temporary symptomatic relief with
topical applications (e.g. corticosteroids), and specific neurological pathways associated with the generation of
chronic itch have not been elucidated. Here, we propose that CHRONIC ITCH, as occurs in Atopic Dermatitis,
involves a novel signaling pathway that ends in release of NPPB by specific neurons in the DRG. Central to
this pathway leading to chronic itch are four molecules: a) thymic stromal lymphopoietin (TSLP); b)
PERIOSTIN c) the (αvβ3) integrin receptor on specific neurons of the DRG called transient receptor potential
vanniloid-1 (TRPV1) neurons; and, as described above, d) natriuretic polypeptide precursor b (NPPB). The
Specific Hypothesis to be addressed is propagation of chronic itch is is initiated by a Th2 type immune response
in the skin related to atopic dermatitis. This causes localized release of the cytokine TSLP from skin keratinocytes
(and perhaps other cell types in the skin) which then, in an autocrine/paracrine fashion, binds to these and other
keratinocytes via the keratinocyte TSLP/IL7R-receptor complex. This binding activates the JAK-STAT pathway
in the keratinocytes, leading to production and release of the protein PERIOSTIN. PERIOSTIN, released by
these keratinocytes, then sets in motion the following itch circuit: Released PERIOSTIN binds to a PERIOSTIN
- binding integrin receptor αvβ3 expressed on a subset of neurons in the dorsal root ganglia, called TRPV1
neurons. As a result of PERIOSTIN binding, these TRPV1 neurons then release the neuropeptide NPPB
centrally in the spinal cord that in response sends itch signals to the brain. We will test this hypothesis through
the following specific aims: Aim 1). To determine if TSLP binding to the specific TSLP receptor complex on
keratinocytes provokes production and release of periostin through activation of the JAK-STAT pathway in these
cells; Aim 2) To determine whether PERIOSTIN binds directly to the integrin receptor αvβ3 on TRPV1 neurons
(NPPB/SST) in the DRG, and whether this generates an itch sensation in vivo; Aim 3) To demonstrate a direct
role of PERIOSTIN and neuropeptide NPPB in the generation of chronic itch in vivo. This proposed research will
identify fundamental mechanisms for neuronal responses during the generation of chronic itch secondary to
inflammatory skin disease. PERIOSTIN, integrin receptor signaling, and/or NPPB – producing neurons may
provide novel therapeutic targets to treat skin diseases manifested by chronic itch.

## Key facts

- **NIH application ID:** 10440372
- **Project number:** 5R01AR077692-02
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** Santosh K. Mishra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $212,636
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440372

## Citation

> US National Institutes of Health, RePORTER application 10440372, Integrin receptor: A connecting link between skin and peripheral sensing neurons in atopic dermatitis (5R01AR077692-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10440372. Licensed CC0.

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