# Crosstalk of Innate and Adaptive Immunity in Infection-Sensitized Neonatal HIE

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $353,281

## Abstract

PROJECT SUMMARY (Description):
 This project seeks to identify the pathogenic actions of microglia and Th17 lymphocytes in
infection-sensitized hypoxia-ischemia (HI) brain injury of newborns, including their interactions
and strategies for intervention. The combination of prenatal infection and hypoxia-ischemia is a
severe threat to immature brains, and often causes death or permanent neurological deficits.
Better understanding the mechanisms of infection-sensitized neonatal HI injury is needed to
design more effective therapies of this important neonatal disorder.
 Based on strong preliminary results, we hypothesize that the combination of systemic
inflammatory responses and HI promotes early onset of Th17 cells in neonatal brains. The Th17
cell cytokines and tPA (tissue plasminogen activator)-mediated sensitization of endotoxin
signaling greatly enhances microglial activation, which not only causes severe brain injury but
also fosters the maturation of Th17 cells. We will test this hypothesis in two specific aims.
 Aim 1 addresses the unique responses of microglia/monocytes to infection-HI and their
effects on Th17 cell maturation.
 Aim 2 addresses the functions Th17 cells in infection-HI and their effects on microglia and
monocyte activation in this condition.
 In sum, this project will determine the mechanisms of microglia-Th17 cell crosstalk in
neonatal infection/HI brain injury, and provide the scientific basis for potential new therapies.

## Key facts

- **NIH application ID:** 9864110
- **Project number:** 5R01NS095064-06
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Chia-Yi Kuan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $353,281
- **Award type:** 5
- **Project period:** 2018-07-09 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9864110

## Citation

> US National Institutes of Health, RePORTER application 9864110, Crosstalk of Innate and Adaptive Immunity in Infection-Sensitized Neonatal HIE (5R01NS095064-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9864110. Licensed CC0.

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