# Novel role for protein kinase D in airway inflammation and antiviral immunity

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2020 · $385,000

## Abstract

Respiratory viruses are a major cause of morbidity and mortality worldwide. After infecting their target
cells, viruses are sensed by different pattern recognition receptors (PRR’s) that initiate innate anti-viral
immune responses. Viral double stranded RNA (dsRNA) is a potent stimulator of innate immunity and
activates toll-like receptor 3 (TLR3) as well as the intracellular helicases RIG-I (retinoic acid-inducible
gene I) and MDA5 (melanoma differentiation-associated protein 5). Double stranded RNA sensors
are expressed by the airway epithelium, and couple to complex downstream signaling pathways that
initiate the expression of interferons and cytokine genes, resulting in airway inflammation and
induction of anti-viral immunity. This R01 application is based on our serendipitous discovery that the
serine/threonine kinase protein kinase D (PKD) has a previously overlooked role in innate immune
responses driven by the dsRNA polyI:C. There are three PKD isoforms (PKD1-3), but little is known
about their expression or function in the lung. Using targeted siRNA knock-down and a new line of
knock-out mice, we found that polyI:C-induced epithelial cytokine gene expression and neutrophil
recruitment to the lung are both dependent on PKD3. This appears to involve a previously unreported
role for PKD3 in polyI:C signaling in epithelial cells, as well as in chemokine receptor signal
transduction in neutrophils. Excitingly, we also discovered that a potent and selective PKD antagonist
protects mice from infection with influenza A virus (IAV). In this revised R01 application, we propose
three Aims that will: explain exactly how PKD mediates dsRNA signal transduction in airway epithelial
cells (Aim 1), use conditional deletion and other strategies to unravel a new neutrophil specific role for
PKD3 in lung inflammation (Aim 2), and test the hypothesis that targeting PKD will attenuate lung
inflammation after influenza infection in mice (Aim 3).

## Key facts

- **NIH application ID:** 9971917
- **Project number:** 1R01AI144241-01A1
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Steve N Georas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,000
- **Award type:** 1
- **Project period:** 2020-03-13 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971917

## Citation

> US National Institutes of Health, RePORTER application 9971917, Novel role for protein kinase D in airway inflammation and antiviral immunity (1R01AI144241-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9971917. Licensed CC0.

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