# The Role of Efferocytosis in Inflammatory Arthritis

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2024 · $201,875

## Abstract

THE ROLE OF EFFEROCYTOSIS IN INFLAMMATORY ARTHRITIS
Abstract
 Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints which affects 1 in 100 people
globally and millions in the US alone. We noted marked presence of apoptotic cells in the inflamed joints of
arthritic mice. Apoptosis is intricately linked with phagocytosis of apoptotic cells, also known as ‘efferocytosis’.
The current dogma suggests that increased apoptotic cell persistence in tissues inevitably leads to pathology.
However, our data presented in this application suggest that this dogma warrants further testing. First, we show
that systemic injection of apoptotic cells effectively alleviates inflammation in arthritic mice. Further, cell-free
apoptotic cell supernatants or even purified apoptotic cell-released metabolites potently suppress inflammatory
arthritis. Finally, pharmacologic or genetic efferocytosis reduction (not complete ablation) also reduce
inflammation in arthritic mice. Here, we will test the hypothesis that reduced efferocytosis alleviates inflammation
in arthritis through increased release of anti-inflammatory mediators (from uncleared apoptotic cells) and
enhanced corpse processing/degradation (due to reduced corpse load in phagocytes). We will pursue the
following aims: 1. Using mice with pharmacologic or genetic decrease in efferocytosis, we will quantify multiple
disease parameters in arthritis, determine the numbers of apoptotic cells in the inflamed joints, analyze the
phagocyte response, and analyze the metabolomics of reduced cell clearance environments. 2. Generate and
validate a new transgenic mouse model with tissue-specific, inducible reduction of efferocytosis. Our findings
will further our understanding of efferocytosis in homeostasis and inflammation and could open new avenues in
therapeutic designs for the treatment of rheumatoid arthritis.

## Key facts

- **NIH application ID:** 10786105
- **Project number:** 5R21AI173639-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Sanja Arandjelovic
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $201,875
- **Award type:** 5
- **Project period:** 2023-02-14 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10786105

## Citation

> US National Institutes of Health, RePORTER application 10786105, The Role of Efferocytosis in Inflammatory Arthritis (5R21AI173639-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10786105. Licensed CC0.

---

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