# Viral and allergen-driven immunity in chronic lung disease

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $671,223

## Abstract

Abstract
Severe allergic asthmatic disease is characterized by significant airway structure changes and chronic
inflammation predominated by eosinophils, mononuclear cells, and lymphocytes, and accompanied by mucus
hypersecretion that depends upon the nature of the immune response. The most severe airways disease
progresses through a continuum of responses ranging from manageable airway dysfunction to a steroid
resistant state that is often a result of a severe exacerbation that is difficult to control. Over the more than 25
years of work in this area my laboratory has defined the role of numerous cytokines and chemokines that
initiate and drive the pulmonary immune responses, identified innate immune molecules that shape the
immune phenotype (TLRs, Notch), defined a role for respiratory viral infections that induce and exacerbate
disease, examined epigenetic regulation of immune cell function, and more recently identified metabolic control
of innate immune cell activation. Many of our previous discoveries have revealed potential therapeutic targets
for pulmonary diseases, including studies in our 2nd NHLBI RO1 that examine stem cell factor and ILC2. One
of our present NHLBI RO1 grants is examining the role of autophagy and cellular metabolism for innate
immune cell function. Our most recent studies are addressing additional mechanisms linked to trained
immunity within the lung, as well as development of lung responses that alter the structural and functional
integrity of the lung. While we will be combining 2 RO1 with divergent themes, our overall objective of
understanding how the pulmonary immune environment is developed and maintained during disease is central
to all of our studies. Together, our past and ongoing investigations are revealing an integrated understanding
of not only the immune responses during disease development, but also the long-term consequence of early
disease and its relationship to altered lung function and development. Using this R35 mechanism, we will
continue expanding on these areas of research that will be paradigm shifting. We will focus on specific goals
including 1) determine how early RSV-induced responses in the lung alter the innate immune cell phenotype
and induce lung structural changes that predisposes the lung to later allergic/asthmatic responses; 2) examine
the role that stem cell factor (SCF) has on altering the activation of ILC2 populations in chronic pulmonary
disease; and 3) investigate how cell metabolism alters immune cell development during disease to maintain
and extend disease severity. Completion of these studies will provide new insights, establish new paradigms,
and complete proof of concept studies needed to advance knowledge and validate new, therapeutically
relevant mechanisms in clinical disease.

## Key facts

- **NIH application ID:** 10773012
- **Project number:** 5R35HL150682-05
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Nicholas W Lukacs
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $671,223
- **Award type:** 5
- **Project period:** 2020-03-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10773012

## Citation

> US National Institutes of Health, RePORTER application 10773012, Viral and allergen-driven immunity in chronic lung disease (5R35HL150682-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10773012. Licensed CC0.

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