# Tissue niches for ILC3 development in newborn's lung

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2021 · $489,715

## Abstract

PROJECT SUMMARY :
Bacterial pneumonia kills more than one million infants around the world each year. Type 3 innate
lymphoid cells (ILC3) are critical for lung mucosal defense against bacterial pneumonia in the
newborns. However, the signals that guide pulmonary ILC3s development are incompletely
understood. A wave of ILC3s accumulate into the newborn lungs during the first week of life
contemporaneous with postnatal lung growth and colonization by commensal microbiota. Clinical
interventions in premature infants, for instance, the use of antibiotics alter microbiota and are
associated with decreased lung ILC3s and increased risk of pneumonia. Similarly, therapies such as
mechanical ventilation and corticosteroids interrupt the postnatal lung growth leading to
bronchopulmonary dysplasia (BPD). Infants with BPD have decreased lung ILC3 and increased
likelihood of morbidity due to respiratory infections. Therefore, understanding this relationship is
clinically important. In published studies, we found that ILC3s localized to the alveoli in the newborn
lungs, where they intimately associated with a subset of Gli1+ stromal cells creating a pulmonary ILC3
niche. Insulin-like growth factor (IGF)1 was an essential component of the pulmonary ILC3 niche. We
found that developmental signals operating in the niche cells instructed the differentiation and
functional fitness of lung ILC3. The convergence of postnatal lung growth and colonization by
commensal microbiota during the `critical window' of the newborn period allows the developing lung
and evolving microbiota to `instruct' rapidly maturing pulmonary mucosal defenses. Such convergence
ensures long-lasting protection against respiratory pathogens. We hypothesize that carefully timed
signals from commensal bacteria act cooperatively with developmentally programmed cues in the
unique lung niches to pattern the immune environment in the lung. The proposed studies will resolve
the following knowledge gaps regarding lung ILC3 development. 1) When is the lung ILC3 niche
endowed during development and how is it maintained throughout childhood (Aim 1)? 2) How does
ILC3 niche instruct the development, differentiation and functional fitness of lung ILC3 (Aim 2) ? 3)
How does the lung niche integrate the signals from commensal bacteria (Aim 3)?
Together, these aims will use developmentally appropriate models to answer a vital and unknown
question: how the newborn's lungs are seeded with ILC3 and how they are regulated at their lung niches
via local and extrapulmonary inputs throughout childhood.

## Key facts

- **NIH application ID:** 10096158
- **Project number:** 1R01HL155611-01
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Hitesh Deshmukh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $489,715
- **Award type:** 1
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10096158

## Citation

> US National Institutes of Health, RePORTER application 10096158, Tissue niches for ILC3 development in newborn's lung (1R01HL155611-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10096158. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*