# Role of dysbiotic commensal bacteria in modulating airway inflammation in a mouse model with human lung immune system

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2020 · $235,875

## Abstract

Abstract
Asthma is a lung disease characterized by recurrent airway hyper-responsiveness, which is often
triggered by type 2 inflammatory cytokines produced by Th2 helper cells or type 2 innate lymphoid
cells. The direction and severity of inflammation is often determined by the pro-inflammatory or
anti-inflammatory cytokines produced by myeloid cells upon sensing of commensal microbiota or
microbial pathogens through pattern recognition receptors. The link between asthma and airway
bacterial communities has been well documented owing to culture-free next generation
sequencing technology. The use of 16s rRNA sequencing methods reveals the dysregulated
airway microbiome in asthmatic patients. However, it lacks insights into how the airway microbiota
manipulate mucosal immune regulations and alter inflammatory status during steady state or
asthma onset. In vivo systems are indispensable to the study of the cross talk between microbiota
and tissue inflammation. Traditional mouse models of asthma are not well-suited to the study of
dysbiotic airway microbiota in asthmatic patients because humans and mice present major
differences in their microbiota, as well as in their immune responses to microorganisms. The rapid
development of studies on asthma and airway microbiome urgently needs novel murine models
to deciphering the underlying interplays between commensal bacteria and mucosal immune
responses and, therefore, to explain the epidemiological findings and translate them into clinical
interventions. We have developed a unique humanized mouse model named MISTRG, in which
several human cytokine coding genes were knocked into their respective mouse loci. MISTRG
mice develop functional human lymphoid and myeloid lineage cells. More importantly, over 90%
of immune cells in the lung of MISTRG mice were human immune cells. In this proposed work,
we will deploy this novel humanized mouse model to investigate the interplay between dysbiotic
airway microbiota and airway inflammation. Upon completion of our proposed work, we will obtain
a comprehensive evaluation on airway microbiota composition and its corresponding
inflammatory signature in this novel humanized mouse model of airway inflammation. Our study
will provide direct evidence on how dysbiotic microbiota can induce or alter airway inflammatory
response to trigger asthma onset. This study will be a breakthrough for current research on
asthma and airway microbiota to help elucidate the complex pathogenesis underlying this disorder
and provide more evidence for microbiota-based asthma prevention and control.

## Key facts

- **NIH application ID:** 9850206
- **Project number:** 5R21AI139649-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** LIANG SHAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $235,875
- **Award type:** 5
- **Project period:** 2019-01-14 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850206

## Citation

> US National Institutes of Health, RePORTER application 9850206, Role of dysbiotic commensal bacteria in modulating airway inflammation in a mouse model with human lung immune system (5R21AI139649-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9850206. Licensed CC0.

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