# Monocyte and macrophage polarization in systemic juvenile idiopathic arthritis and macrophage activation syndrome.

> **NIH NIH K08** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $637

## Abstract

PROJECT SUMMARY / ABSTRACT
Systemic juvenile idiopathic arthritis is a severe inflammatory disease of childhood conferring significant
risk for fatal complications including Macrophage Activation Syndrome (MAS). The phenotype and function of
the key effector monocytes and macrophages in systemic JIA remains unclear. These cells adopt distinct
polarization states based on specific activating signals, modified by microRNA to “fine-tune” these
transcriptional responses. Circulating monocytes in systemic JIA appear to display a unique mixed polarization
phenotype, and little is known regarding how tissue resident macrophages are further altered during
emergence of MAS. Notably, despite effective treatment children with systemic JIA remain at risk for MAS.
Thus, there is a critical need to characterize the phenotype of monocytes and tissue macrophages in systemic
JIA, and particularly how they contribute to emergence of MAS. In the absence of such knowledge, developing
novel strategies to effectively prevent and treat MAS will remain a formidable challenge. The objective in this
application is to define polarization-specific gene expression signatures and functional roles of microRNA in
monocytes and macrophages from children with systemic JIA and a mouse model of systemic JIA/MAS. Our
central hypothesis is monocytes from children with systemic JIA have a distinct polarized pattern which is
regulated by microRNA, and further dysregulated during MAS. The research plan described in this application
has three Specific Aims: to define polarization-specific and single-cell gene expression profiles in peripheral
monocytes and bone marrow macrophages from systemic JIA and MAS patients (Aim 1), to identify specific
molecular pathways targeted by microRNA that are essential for monocyte and macrophage polarization in
these disorders (Aim 2), and to determine gene expression signatures and microRNA-mediated functions of
polarized myeloid populations in a mouse model of MAS (Aim 3). These independent and complementary
aims will utilize emerging technologies such as microRNA expression profiling and single-cell RNAseq to
define the molecular control of polarization-specific transcriptional signatures in monocytes and macrophages
in children with systemic JIA and MAS. Together these findings are expected to have positive translational
impact, through providing new targets to modulate inflammation in systemic JIA and impact the risk for MAS.
 Dr. Grant Schulert is currently an Instructor of Pediatrics in the Division of Rheumatology at Cincinnati
Children's Hospital Medical Center. Dr. Schulert's long-term goal is to develop an independent research career
as a pediatric rheumatologist focused on the pathogenesis and novel treatment approaches for inflammatory
disorders. In the completion of these proposed aims, Dr. Schulert will draw upon greater than 10 years'
experience studying inflammation and innate immunity, but will also gain new skills and knowledge in the ...

## Key facts

- **NIH application ID:** 10076034
- **Project number:** 3K08AR072075-03S1
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Grant Sanford Schulert
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $637
- **Award type:** 3
- **Project period:** 2017-08-07 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10076034

## Citation

> US National Institutes of Health, RePORTER application 10076034, Monocyte and macrophage polarization in systemic juvenile idiopathic arthritis and macrophage activation syndrome. (3K08AR072075-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10076034. Licensed CC0.

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