# Mast cells in skin innate immune defense

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $44,818

## Abstract

Abstract
The multifunctional nature of mast cells (MCs) has been revealed through their
involvement in both innate and adaptive immune responses. Recent insight into the
various functions of MCs has shown that these innate immune effectors possess the
dual ability to kill microbes and to modify classical adaptive immune responses.
Members of the cathelicidin family of antimicrobial peptides (AMPs) are expressed by
MCs and epithelial cells at sites of injury. The granular localization of the cathelicidin
peptides, their extracellular release, and their capacity to modify inflammatory responses
suggests that cathelicidin plays an important role in the capacity of MCs to combat skin
infection. Preliminary data inside this proposal show that MCs are sentinels in the skin
for defending against bacterial and viral infections. Mast cell-deficient (KitW-sash-/-) mice
are more susceptible to skin infection than the wild-type mice, while KitW-sash-/- mice
reconstituted with skin MCs show a normal response. Using MCs derived from mice
deficient in cathelicidin, we showed that antimicrobial peptides (AMPs) are critical anti-
pathogenic granule components. Signaling through toll-like receptor (TLR)-2 increased
the level of antimicrobial peptide MCs, enhancing their capacity to fight skin infections.
 The central hypothesis of this proposal is that MCs play a seminal role in the skin
innate immune response to infections by orchestrating other cell responses and
expressing cathelicidin peptides. Several of the experiments will focus on establishing
how MCs modify skin microenvironment and coordinate with other cells to respond to
infection (Aim 1). Once the contribution of MCs in skin innate immune defense has been
elucidated, Aim 2 will examine the regulation and function of MC AMPs during skin
infections. Understanding the role of MCs in skin defense against foreign pathogens will
suggest new therapeutic targets for combating infection.

## Key facts

- **NIH application ID:** 10076271
- **Project number:** 3R01AI093957-07S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Anna Di Nardo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $44,818
- **Award type:** 3
- **Project period:** 2011-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10076271

## Citation

> US National Institutes of Health, RePORTER application 10076271, Mast cells in skin innate immune defense (3R01AI093957-07S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10076271. Licensed CC0.

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