# SLAMF7 Regulates Synovial Macrophages in Rheumatoid Arthritis

> **NIH NIH K08** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $177,120

## Abstract

Abstract
Macrophages are central to the pathology in rheumatoid arthritis, driving inflammation in joints of affected
patients, but there are currently no therapies available that specifically target macrophages. In this proposal,
we seek to characterize hallmark pathways of macrophage dysregulation in arthritis by understanding
immunomodulatory receptors that regulate macrophage activation states. In our preliminary data, we have
analyzed RNA sequencing on synovial macrophages from a large cohort of patients with arthritis to identify
genes that may regulate macrophages in arthritis. Within this dataset, SLAMF7 expression in macrophages
was highly associated with disease activity and inflammation. This receptor is expressed by leukocytes and
controls their activation through homotypic interactions with SLAMF7 on other cells. A cytoplasmic
immunoreceptor tyrosine switch motif (ITSM) can drive either activation or inhibition of cells through this
receptor, depending on the cell type and its activation state. However, the role of this receptor on macrophages
is not well understood. Based on preliminary data suggesting that activation of this pathway drives
inflammatory cytokine secretion, we hypothesize that SLAMF7 drives macrophage activation, amplifying
inflammation within the joints of patients with arthritis. This research proposal is focused on understanding how
SLAMF7 regulates the activation state of macrophages and to define its contribution to inflammatory arthritis.
We will study the role of this receptor on macrophages using human cells (Aim 1) and mouse models of
arthritis (Aim 2). We will use in vitro assays to determine how SLAMF7 regulates the activation of
macrophages from blood and synovial tissue by quantifying changes in cytokine production, surface activation
marker expression, and transcriptomic changes. We will further evaluate the function of this gene in vivo by
using mice that are deficient for SLAMF7, in the germline and specifically in macrophages, in models of
inflammatory arthritis. We expect that these studies will provide key insights into how SLAMF7 regulates the
activation state of synovial macrophages, which may lead to new therapeutic strategies targeting this pathway.
In addition to groundbreaking discoveries about how SLAMF7 regulates macrophage function in arthritis, this
project will provide the candidate with key skills in computational analyses and mouse models of arthritis that
will allow him to progress to become a successful physician scientist leading research to understand the
pathways of macrophage dysfunction in arthritis.

## Key facts

- **NIH application ID:** 10242919
- **Project number:** 5K08AR075850-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Daimon P. Simmons
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $177,120
- **Award type:** 5
- **Project period:** 2019-09-26 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242919

## Citation

> US National Institutes of Health, RePORTER application 10242919, SLAMF7 Regulates Synovial Macrophages in Rheumatoid Arthritis (5K08AR075850-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242919. Licensed CC0.

---

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