# Role of SCARF1 in removal of apoptotic debris and protection against autoimmunity

> **NIH NIH R21** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2022 · $209,375

## Abstract

Project Summary
Efficient detection and clearance of apoptotic cells is essential in the maintenance of immune
tolerance and tissue homeostasis. Phagocytes are responsible for removal of dying cells;
however, defects in recognition or engulfment of apoptotic cells can lead to chronic inflammation
and autoimmune disease. Accumulation of apoptotic cells in tissues has been associated with the
autoimmune disease systemic lupus erythematosus (SLE), and several receptors on phagocytes
responsible for the clearance of apoptotic debris have been identified. We previously identified
the scavenger receptor expressed on endothelial cells-1 (SCARF1) as the receptor for apoptotic
cells on dendritic cells via interactions with C1q/phosphatidylserine complexes on the dead cells
(Ramirez-Ortiz et.al.; Nature Immunology). Loss of SCARF1 results in impaired uptake of
apoptotic cells in vitro and in vivo, with accumulation of cell corpses in tissues and blood.
Consequently, SCARF1-deficient mice develop lupus-like autoimmune disease. Our previous
findings revealed that SCARF1 is a non-redundant efferocytosis receptor; however, additional
work is needed to identify the mechanisms necessary for SCARF1-mediated removal of apoptotic
cells and prevention of spontaneous autoimmunity in vivo. We hypothesize that SCARF1 plays
an essential role in the physiological clearance of apoptotic debris, and that dysregulated or loss
of SCARF1 expression on phagocytes leads to impaired AC uptake, loss of immune self-tolerance
and development of autoimmunity. We propose to define the domains in SCARF1 that mediate
recognition, signaling and removal of apoptotic cells and determine the relative contribution of
SCARF1 in radioresistant cells vs hematopoietic cells. A comprehensive understanding of all the
processes required for effective apoptotic cell removal can identify new targets not only for Lupus,
but for many autoimmune, metabolic and infectious diseases.

## Key facts

- **NIH application ID:** 10409829
- **Project number:** 5R21AI163765-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Zaida Gisela Ramirez-Ortiz
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $209,375
- **Award type:** 5
- **Project period:** 2021-05-24 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10409829

## Citation

> US National Institutes of Health, RePORTER application 10409829, Role of SCARF1 in removal of apoptotic debris and protection against autoimmunity (5R21AI163765-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10409829. Licensed CC0.

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