# Origins and functional roles of Miwi2-positive multiciliated cells during inflammation

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $412,500

## Abstract

ABSTRACT
We have identified a subset of ciliated cells (30%) in the mouse and human airways that express MIWI2,
a protein only previously observed in the mouse testes where it functions to suppress transposon
transcription. Newly generated ontogeny data along with global transcriptomic and gene ontology
analyses of mouse MIWI2-positive (MPACs) and negative ciliated cells (non-MPACs) further support
the concept of multiciliated cell heterogeneity and our overall hypothesis: MIWI2-positive expression
distinguishes 2 distinct ciliated cell lineages in the airway. For the first time, these data hint at
functionally distinct multi-ciliated cell subsets and suggest new lineage models for the airway epithelium.
In view of the broader implications of this work for the field, our over-riding objective and focus in this
revised grant are to develop and elucidate a basic understanding of the differential biology of these 2
subtypes of ciliated cells in the mouse airway. As a result, many of our studies are now deliberately and
logically directed at characterizing the ontogeny, half-life, and origins of MPACs relative to non-MPACs.
Our data also indicate that ciliated cells play a distinct role in regulating inflammation during injury, a
function not generally ascribed to this cell type. Determining the relative role of MPACs and non-MPACs
and ciliated MIWI2 in regulating inflammatory states in the lung are thus important sub-goals of this
proposal. In our view, identifying immune-regulatory roles for ciliated cells has not been sufficiently
addressed since most of the research on this cell type has traditionally concentrated on their mechanical
contributions to mucus clearance. As such, this direction lends a deeper and more expansive
significance to our proposed studies. By using several unique genetic mouse models that sustain the
identification, tracking, and fate of ciliated cells, including MPACs, we propose to examine our
hypothesis and meet our goals in 3 Aims. In Aim 1 we well establish the ontogeny of MPACs, their
lineage relationship to non-MPACS and their half-life during lung homeostasis. In Aim 2, we will identify
the origin of new MPACs that arise during airway remodeling after lung infection and during MPAC-
specific cell regeneration. In Aim 3, we will determine the relative roles of MIWI2 protein and MPACs
in the host response to early lung inflammation and infection. Together, these studies will forge new
directions in the fundamental biology of the airway by establishing a new understanding of epithelial cell
lineages and by integrating and connecting the fields of Piwi proteins, inflammation, and multiciliated
cells of the lung.

## Key facts

- **NIH application ID:** 10129992
- **Project number:** 5R01HL136725-04
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Alan Fine Fine
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $412,500
- **Award type:** 5
- **Project period:** 2018-03-07 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129992

## Citation

> US National Institutes of Health, RePORTER application 10129992, Origins and functional roles of Miwi2-positive multiciliated cells during inflammation (5R01HL136725-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10129992. Licensed CC0.

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