# Eosinophils in Bullous Pemphigoid

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $367,552

## Abstract

Project Summary
Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease characterized by autoantibodies
and an inflammatory infiltrate at the lesional site. BP autoantibodies belong to IgG and IgE isotypes and
recognize two hemidesmosomal proteins, BP180 and BP230. These autoantibodies mainly target the NC16A
extracellular domain of BP180. The dermal infiltrate contains eosinophils, neutrophils, mast cells, macrophage
and lymphocytes, with eosinophils being the predominant cell type. The roles of anti-BP180 IgG autoantibodies
and neutrophils in BP have been extensively investigated. In vitro and in vivo studies have demonstrated that
anti-BP180 NC16A IgG autoantibodies fix complement, recruit neutrophils and cause BP-like blisters.
However, roles of anti-BP180 IgE and eosinophils in BP remain largely unknown. Lack of a suitable animal
model is a major obstacle for studies of IgE and eosinophils because human IgE do not recognize mouse IgE
receptors. Our lab currently developed a double humanized mouse stain (termed hFcεRI/NC16A mice), in
which the human NC16A domain replaced the mouse counterpart NC14A domain and human FcεRI are
expressed on eosinophils and mast cells. More significantly, adult hFcεRI/NC16A mice injected with anti-
NC16A IgE autoantibodies from BP patients develop BP skin disease that required eosinophils and mast cells.
The objective of this proposal is to study the role of eosinophils and mast cells in BP using our newly
developed hFcεRI/NC16A mouse model. The overall goal of this project is to increase our understanding of the
innate immunity of BP and how it relates to the functions of innate immune system players in inflammation and
autoimmunity. In this grant proposal, we will determine how eosinophils are recruited and functionally interact
with mast cells (Aims 1 and 2). Proteolytic enzymes from these innate immune cells are critical for skin tissue
injury, therefore, we will translate our animal model findings to human BP (Aim 3). Since this proposal
integrates both disease mechanism studies and preclinical trials, the findings are expected to have a significant
impact on the treatment of patients with BP.

## Key facts

- **NIH application ID:** 10198769
- **Project number:** 5R01AR070276-05
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Zhi Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $367,552
- **Award type:** 5
- **Project period:** 2017-07-24 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10198769

## Citation

> US National Institutes of Health, RePORTER application 10198769, Eosinophils in Bullous Pemphigoid (5R01AR070276-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10198769. Licensed CC0.

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