# Epigenetic changes to the IL-17 promoter landscape in neutrophils

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $235,375

## Abstract

Abstract
 IL-17A (IL-17) is a pro-inflammatory cytokine that is secreted primarily by lymphoid cells, including
CD4+ Th17 cells, γδ T cells, natural T cells and innate lymphoid cells (ILC17), and is induced following
fungal and bacterial infections, and in autoimmune disease. IL-17 activates receptors on endothelial and
epithelial cells to produce CXC chemokines such as IL-8, which is chemotactic for neutrophils. There are
also multiple reports that neutrophils produce IL-17 in infected and autoimmune individuals, and in murine
models of infection and autoimmunity. However, a recent study showed that the IL-17 locus is not in an
active status in human neutrophils (Cassatella 2018). We reported Il17a gene expression in neutrophils
during Aspergillus infections, and in neutrophils from fungal infected patients and healthy individuals in India,
but not in healthy individuals in the USA. We therefore suggest that long-term exposure to fungal spores is a
potential mediator of epigenetic modifications in neutrophils that results in accessibility of the IL-17 gene
locus. We therefore propose to examine IL-17 promoter accessibility and histone modifications in this region
using ATAC sequencing and ChIP-PCR in neutrophils from fungal infected patients in India compared with
healthy individuals in the USA. Rheumatoid arthritis patients also produce IL-17 (Ortiz-Navarrete, 2019),
indicating that chronic inflammation also leads to epigenetic modifications in the Il17a locus. Under
conditions where the IL-17 locus is accessible, we will identify which transcription factors bind to this region.
Epigenetic studies will also be conducted in Aspergillus infected and immunized mice that produce IL-17+
neutrophils, and we will use single cell RNA sequencing to characterize sub populations of IL-17+
neutrophils. Together, results of the proposed studies will identify the molecular events that underlie
epigenetic regulation of IL-17 in neutrophils.

## Key facts

- **NIH application ID:** 10058179
- **Project number:** 1R21AI149239-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Eric Pearlman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $235,375
- **Award type:** 1
- **Project period:** 2020-06-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10058179

## Citation

> US National Institutes of Health, RePORTER application 10058179, Epigenetic changes to the IL-17 promoter landscape in neutrophils (1R21AI149239-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10058179. Licensed CC0.

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