# Microbial regulation of the keratinocyte AHR

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $534,967

## Abstract

PROJECT SUMMARY
The complexity of microbial communities inhabiting the healthy human skin have been illuminated in recent
years, as well as signatures associated with inflammatory skin diseases such as atopic dermatitis. However,
the molecular and biochemical mechanisms that mediate microbial symbiosis with the skin are not well
understood. We recently found that homeostatic skin barrier function, epidermal differentiation, and recovery
from injury are dependent on the microbiota in mice. These effects were mediated by the keratinocyte aryl
hydrocarbon receptor (AHR). The AHR is a ligand-dependent xenobiotic receptor of foreign/toxic substances
that is also known to regulate epidermal differentiation, tight junction/adhesion, and antimicrobial innate
immune responses. The objective of this project is to identify and characterize microbial ligands of the AHR,
and to test their utility in treating skin barrier dysfunction and infection. Epidermal barrier dysfunction is a key
feature of atopic dermatitis, a common skin disorder characterized by chronic and relapsing, itchy, inflamed,
skin lesions and dysbiotic microbiota. To test the hypothesis that commensal bacteria mediate AHR signaling
to promote skin barrier integrity and defense, we propose three aims. 1) Define microbial mechanisms of
keratinocyte AHR regulation that promote barrier repair; 2) Establish pharmacodynamic actions of microbial
AHR ligands to promote skin barrier function and antimicrobial defense; and 3) Evaluate microbial AHR ligands
in treatment of epidermal barrier dysfunction and S. aureus infection in murine models. Findings from these
studies will provide novel, accessible targets to promote skin barrier function and repair, while advancing
fundamental understanding of cutaneous host-microbiota interactions.

## Key facts

- **NIH application ID:** 10808055
- **Project number:** 5R01AR079856-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Elizabeth Anne Grice
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $534,967
- **Award type:** 5
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10808055

## Citation

> US National Institutes of Health, RePORTER application 10808055, Microbial regulation of the keratinocyte AHR (5R01AR079856-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10808055. Licensed CC0.

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