# Mechanoregulation of the epidermal immune response: the role of desmoglein 1

> **NIH NIH F32** · NORTHWESTERN UNIVERSITY · 2021 · $68,562

## Abstract

Project Summary
The epidermis of the skin provides an essential barrier between the organism and the environment. Disruption
of the epidermal barrier is associated with chronic inflammatory diseases such as psoriasis and atopic dermatitis.
Affected areas in patients with these diseases are frequently distributed in regions that experience higher
amounts of mechanical stress, such as the extensor areas in psoriasis and flexor regions in atopic dermatitis.
The underlying basis of sensitivity to mechanical stress in these diseases is unknown. Desmosomes are
intercellular junctions that are critical for both formation of the barrier and for providing mechanical strength to
the epidermis and are abundant in tissues that experience large amounts of mechanical stress. The desmosomal
cadherin Desmoglein 1 (Dsg1) is only expressed in stratified epithelium such as the epidermis and is critical for
proper epidermal development and function. Mutations in Dsg1 causes severe dermatitis, multiple allergies and
metabolic wasting (SAM) syndrome, a chronic inflammatory disease associated with recurrent skin infections,
abnormal epidermal differentiation and loss of adhesion between keratinocytes. Barrier defects in these patients
may explain some of the inflammation present in the skin; however, isolated keratinocytes continue to express
increased proinflammatory cytokine levels in cell culture. Knockdown of Dsg1 in normal primary keratinocytes
also causes an increase in proinflammatory cytokine expression. These data raise the possibility that Dsg1
contributes to inflammatory responses. Other evidence indicates that Dsg1 may act as a stress sensor. Dsg1 is
downregulated by several types of environmental stress, including exposure to UV. Preliminary data show that
Dsg1 is downregulated in differentiated keratinocytes exposed to mechanical stress. Mechanical stress also
increases expression of proinflammatory cytokines in keratinocytes, many of which overlap with those increased
in keratinocytes after knockdown of Dsg1. This proposal will test the hypothesis that Dsg1 is a mechanical
stress sensor and regulates epidermal inflammatory responses. Aim 1 seeks to identify the mechanism by
which Dsg1 regulates cytokine expression in keratinocytes. This aim will also test the extent to which the
downregulation of Dsg1 in response to mechanical stress regulates increased cytokine expression. Aim 2 will
determine the molecular mechanism by which mechanical stress downregulates Dsg1 levels in keratinocytes.
Preliminary data indicate that Dsg1 is also downregulated in response to oxidative stress, and the extent to which
increased oxidative stress induced by mechanical insult downregulates Dsg1 will be tested. Increasing our
knowledge of mechanisms by which mechanical stress drives inflammatory responses will improve our
understanding of diseases such as psoriasis and atopic dermatitis, and potentially identify new targets for
developing more effective therapies.

## Key facts

- **NIH application ID:** 10314801
- **Project number:** 1F32AR078645-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Quinn Roth-Carter
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,562
- **Award type:** 1
- **Project period:** 2021-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314801

## Citation

> US National Institutes of Health, RePORTER application 10314801, Mechanoregulation of the epidermal immune response: the role of desmoglein 1 (1F32AR078645-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10314801. Licensed CC0.

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