# Targeting the CHRNA7 Receptor to Modulate Wound Antimicrobial Responses

> **NIH NIH R21** · LOYOLA UNIVERSITY CHICAGO · 2020 · $201,300

## Abstract

#7 PROJECT SUMMARY
Skin wound bacterial infections pose a significant health care burden in the US. They are frequently caused by
Staphylococcus aureus and can be worsened by secondary complications like bacteremia. Of note, males
have a 2-fold higher incidence of S. aureus infection than females in the US. While the higher susceptibility to
S. aureus infection in males can also be observed in mice, reasons for this sex dimorphism are not well
defined. What is known is that optimal host responses to wound infection need balanced pro- and anti-
inflammatory signals by skin and resident immune cells. For example, neutrophil influx to help clear infections
is facilitated by Toll-like receptor (TLR)-dependent pro-inflammatory cytokines and antimicrobial peptide (AMP)
secretion by keratinocytes. Consequently, dysregulation or sex dimorphisms of any these host responses
would negatively affect wound infection outcomes. In fact, our lab has established in the last several years that
overactivation of the nicotinic acetylcholine receptor (nAChR) subtype CHRNA7 may play a prominent role in
impairing the host defense against skin infection in mice and humans by lowering TLR2-mediated
inflammation, AMP production, and neutrophil influx to the wound infection site. However, the relative
contribution of keratinocyte CHRNA7 vs. immune cell CHRNA7 to this host response suppression is unknown.
We have also not elucidated the CHRNA7-dependent downstream signaling mechanism(s) leading to the
above phenotypes and not examined sex dimorphisms in CHRNA7 responses in the context of skin
inflammation and wound infection. In this proposal, we will address two specific aims. 1) We will test our
hypotheses that keratinocyte CHRNA7 is a major player in dampening wound antimicrobial responses and
immune cell recruitment in a sex specific manner, which is supported by our pilot data. 2) We will elucidate the
signaling mechanisms by which keratinocyte CHRNA7 impairs TLR2-mediated the production of
immunomodulatory factors that are necessary for downstream neutrophil antimicrobial responses in vitro. Our
studies will begin to unravel a fundamentally new mechanism by which keratinocyte CHRNA7 modulates
wound antimicrobial responses in a sex specific manner and may be the basis for establishing CHRNA7 as a
novel target for pharmacologic interventions that are designed to improve wound healing outcomes in both
men and women.

## Key facts

- **NIH application ID:** 9896364
- **Project number:** 1R21AR073988-01A1
- **Recipient organization:** LOYOLA UNIVERSITY CHICAGO
- **Principal Investigator:** Katherine Amanda Radek
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $201,300
- **Award type:** 1
- **Project period:** 2020-01-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896364

## Citation

> US National Institutes of Health, RePORTER application 9896364, Targeting the CHRNA7 Receptor to Modulate Wound Antimicrobial Responses (1R21AR073988-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9896364. Licensed CC0.

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