# Characterization of a dendritic cell specific receptor critical for SJS

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $409,375

## Abstract

Project Summary
 The goal of our research is to understand the cellular and molecular mechanisms behind the
development of Stevens-Johnson syndrome. Adverse drug reactions (ADRs) are a serious drug safety concern
that can be hard to predict and treat. Stevens-Johnson syndrome (SJS) is one of the most serious and life-
threatening ADRs characterized by keratinocyte cell death and mucosal breakdown; patients often form lesions
on their palms of hands and soles of their feet and blistering and necrosis of their eyelids, conjunctiva and
cornea. The exact cellular and molecular mechanisms behind drugs triggering SJS is unknown. Using a Ca2+
imaging assay, we found certain members of the Mrgpr GPCR family are activated by multiple known SJS-
causing drugs. To examine the immune effects of these SJS drugs, we developed a novel mouse treatment
where daily oral ingestion of a SJS-causing drug resulted in WT mice forming mucosal secretion in their eyes
and blister bleeding in their hindpaws, similar to symptoms seen in patients suffering from SJS. We generated
a mouse line where the specific Mrgpr's open reading frame was deleted and replaced with GFP and this
genetic removal prevented formation of the SJS-like phenotype. Strikingly, heterozygous Mrgpr +/GFP mice,
mice retaining 1 functional copy of the certain Mrgpr allele, developed the SJS-like phenotype, implying an
important role for this Mrgpr in drug-caused SJS. Further experiments revealed the Mrgpr was expressed in a
subset of dendritic cells, cells known to play an important role in antigen-presentation and immune response
initiation. In this proposal, we will use molecular, cellular, genetic approaches and a potential novel in vivo
animal model to uncover the role of the Mrgpr-expressing dendritic cells in drug-activated SJS. Aim I will focus
on establishing our novel drug-induced SJS mouse model. We will examine what immune changes occur as
mice are dosed with specific SJS-causing drugs and then we will determine what role the specific Mrgprs play
in these immune responses. In Aim II, we will examine the specific characteristics of Mrgpr-expressing
dendritic cells. We will find what type of dendritic cell expresses the Mrgprs and the role they play in the
immune system. We will then examine how the cells change upon exposure to SJS-causing drugs and how
these changes cause a cytotoxic immune response and SJS phenotype. We will also confirm the pivotal role
these Mrgpr-expressing cells play in the development of SJS by rescuing the phenotype in the Mrgpr KO
mouse. In Aim III, we will continue examining the immune cascade triggered by the SJS drugs. Dendritic cells
are known for their important role of presenting antigens to T cells, which activate and in turn cause an immune
response. We will determine what T cells are being activated by the Mrgpr-expressing dendritic cells and what
cellular effects and mediators are released by these activated T cells. We will establish the necessity of T cells...

## Key facts

- **NIH application ID:** 9982185
- **Project number:** 5R01AI135186-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Xinzhong Dong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $409,375
- **Award type:** 5
- **Project period:** 2018-08-16 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982185

## Citation

> US National Institutes of Health, RePORTER application 9982185, Characterization of a dendritic cell specific receptor critical for SJS (5R01AI135186-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9982185. Licensed CC0.

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