# MicroRNA Networks in self-sustaining type 2 airway niches in asthma

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $542,592

## Abstract

Project Summary
 Th2 high asthma is defined by persistent airway inflammation that is driven by cytokine crosstalk between
epithelial cells and tissue resident innate and adaptive immune cells. The central theme of our collaborative
research program is that the focal nature of type 2 inflammation that occurs in asthma reflects the development
of persistent type 2 airway niches containing reprogrammed epithelial and immune cells. Disrupting these niches
may durably impact asthma pathogenesis. Under normal conditions, transient type 2 responses operate to
maintain epithelial barrier function. In asthma, regulatory mechanisms that dampen these responses fail, and
type 2 inflammation with epithelial cell reprogramming and mucin hypersecretion persists at focal sites in the
airways. The central objective of this project is to define molecular determinants of cell reprogramming that
sustain persistent immunopathology in Th2-high asthma.
 The proposed studies focus on two cell types whose programming directly affects this pathological process:
T regulatory (Treg) cells and airway epithelial cells. Our approach builds upon preliminary data indicating that
type 2 inflammation and lung dysfunction correlate inversely with the frequency of a subset of airway Tregs, and
the positive identification of distinct miRNA families that control the programming of Tregs and epithelial cells.
The project is organized into three aims: In Aim 1, we will use single cell sequencing, mRNA and miRNA profiling
and mass cytometry to define airway Treg populations, and to compare Treg subsets in persistent airway type 2
niches marked by focal sites of mucus impaction with those that populate unaffected airways. In Aim 2, we will
dissect Treg programming using miRNA-directed pathway discovery, a novel experimental framework for probing
miRNA:target gene networks. A similar approach will be applied in human airway epithelial cells in Aim 3 to
reveal miRNA:target networks that control the cell reprogramming and mucin hypersecretion that marks airway
type 2 niches in asthma. If successful, the proposed research will uncover novel genes and pathways critical to
the pathology of asthma, advance our understanding how immune regulation mechanisms fail in type 2 airway
niches, and suggest strategies to disrupt the inflammation that sustain this disease.

## Key facts

- **NIH application ID:** 10226877
- **Project number:** 5P01HL107202-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Karl Mark Ansel
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $542,592
- **Award type:** 5
- **Project period:** 2012-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10226877

## Citation

> US National Institutes of Health, RePORTER application 10226877, MicroRNA Networks in self-sustaining type 2 airway niches in asthma (5P01HL107202-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10226877. Licensed CC0.

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