# PATHOGENESIS OF PRISTANE-INDUCED LUPUS

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2021 · $379,760

## Abstract

Project Summary/Abstract
Systemic lupus erythematosus (SLE) is characterized by a variety of clinical and immunological
manifestations. This proposal focuses on an animal model of lupus, pristane-induced lupus,
which recapitulates many of the key features of human SLE including impaired phagocytosis of
dead cells and their recognition by receptors of the innate immune system such as toll-like
receptor 7 (TLR7). TLR7-stimulated proinflammatory cytokine production plays an important role
in autoantibody production, nephritis, arthritis, and the hematological manifestations of lupus.
However, preliminary studies suggest that diffuse alveolar hemorrhage (DAH) is TLR and
cytokine independent and also independent of inflammasomes, suggesting that novel
mechanisms are involved in lung inflammation. The long-term objective is to define the
abnormal immunological pathways responsible for the clinical features of SLE. The central
hypothesis is that lupus in pristane-treated mice and SLE patients is caused by impaired/altered
phagocytosis of apoptotic cells, leading to inappropriate activation of several inflammatory
pathways, which precipitate various aspects of the clinical syndrome. Three Specific Aims are
proposed: Aim 1 addresses the mechanism of inflammation in DAH, examining the contribution
of monocyte/macrophage subsets to the pathogenesis of lung inflammation. Aim 2 addresses
how pristane impairs the phagocytosis of dead cells by macrophages, leading to chronic
inflammation instead of the normal anti-inflammatory response. Aim 3 examines the relevance
of pristane-induced lupus to the pathogenesis of inflammation and DAH in lupus patients. Taken
together, these Aims will provide a more complete picture of why apoptotic cells are removed
inefficiently in SLE patients and how this promotes chronic inflammation, autoimmunity, and
tissue damage. Delineating the signaling pathways activated when dead cells are recognized by
different macrophage subsets may suggest approaches to correct the phagocytic defect in SLE
and/or treat its consequences. In particular, these studies may lead to new strategies for
treating DAH, a complication of lupus that is fatal in over 50% of patients.

## Key facts

- **NIH application ID:** 10231120
- **Project number:** 5R01AR044731-24
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** WESTLEY H REEVES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $379,760
- **Award type:** 5
- **Project period:** 1997-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10231120

## Citation

> US National Institutes of Health, RePORTER application 10231120, PATHOGENESIS OF PRISTANE-INDUCED LUPUS (5R01AR044731-24). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10231120. Licensed CC0.

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