# Neutrophil-mediated pathways of kidney injury in lupus nephritis

> **NIH NIH P20** · DARTMOUTH COLLEGE · 2022 · $307,158

## Abstract

Systemic lupus erythematosus (lupus) is a multi-organ autoimmune disease with 5-10% mortality in 10 
years. Both skin and kidney (lupus nephritis, LN) are severely affected and sensitivity to ultraviolet (UV) 
sunlight rays affecting ~ 80% of patients can lead to LN flares. The cellular and molecular mechanisms 
linking skin inflammation caused by UV light and kidney injury are unknown. The overall objectives in this 
proposal are to: (i) demonstrate mechanisms by which neutrophils migrating from UV-exposed skin 
damage glomerular and tubular cells to trigger LN flares, (ii) elucidate the role of a novel CD177high 
neutrophil population in kidney injury, and (ii) define the role of UV-induced type I interferon (IFN-I) 
response on neutrophil interactions with and damage of kidney structural cells, on a single-cell basis. The 
central hypothesis is that neutrophils recruited to the kidney following skin UV exposure mediate acute 
podocyte and distal tubular loss and injury, and lead to chronic mesangial fibrosis potentiated by type I 
interferon. The rationale for this project stems from the gap in the knowledge of how neutrophils mediate 
kidney injury in lupus. The central hypothesis will be tested by pursuing two specific aims: 1) Define the 
mechanisms of neutrophil-mediated lupus nephritis flares caused by skin exposure to UV light and 2) 
Define the role of UV-induced IFN-I on neutrophil interactions with and damage of kidney structural cells. 
In Aim 1, single cell RNA sequencing (scRNAseq)of renal structural cells, multiplexed immunofluorescence 
staining of the kidney tissue, and kidney proteomics, will be applied to define how neutrophils (e.g., 
CD177hi) injure renal endothelium and epithelium in an autoantibody-mediated and a photosensitive 
model of LN. In Aim 2, scRNAseq of kidney structural cells and neutrophils, in the absence of global or 
neutrophil-specific IFN-I signaling, will define IFN-I driven genes and pathways, as well as 
neutrophil-kidney cells ligand-receptor interactions, involved in UV-triggered kidney injury in LN models. 
The research proposed in this application is innovative because it will identify molecular and cellular 
targets that link local skin and distal renal injury. The proposed research is significant because it is 
expected to provide a strong scientific rationale to target specific pathways of neutrophil-mediated 
inflammatory mechanisms and downstream structural cell injury for therapeutic purposes in LN flares.

## Key facts

- **NIH application ID:** 10692352
- **Project number:** 5P20GM130454-04
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Sladjana Skopelja-Gardner
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $307,158
- **Award type:** 5
- **Project period:** 2022-08-22 → 2023-05-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10692352

## Citation

> US National Institutes of Health, RePORTER application 10692352, Neutrophil-mediated pathways of kidney injury in lupus nephritis (5P20GM130454-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10692352. Licensed CC0.

---

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