# Identification and Functional characterization of circulating exomeres in systemic lupus erythematosus

> **NIH NIH U19** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $205,431

## Abstract

Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that displays highly heterogeneous
clinical and biological manifestations. It is characterized by an excessive production of type I interferon (IFN)
and proinflammatory cytokines, breakdown of tolerance to self-nucleic acids, and development and deposition
of immune complexes in multiple organs. Beyond these hallmarks, metabolic abnormalities, such in glycolysis
and mTOR signaling, in different types of immune cells, such as T cells, macrophages, dendritic cells (DCs)
and neutrophils have been reported. Despite these pathological events, SLE remains an incurable disease
highlighting the clinical unmet need for improved molecular biomarkers for patient treatment stratifications and
advances in developmental therapeutics to combat the disease process.
Cells secrete a wide variety of soluble factors and extracellular particles to mediated intercellular
communication under both physiological and pathological conditions. Emerging evidence suggests that
secreted factors influence specific functions in autoimmune diseases. By employing the state-of-art
asymmetric-flow field-flow fractionation (AF4) technology, we have identified a novel population of non-
membranous nanoparticles termed ‘exomeres’ (~35 nm), which is indeed the predominant nanoparticles
secreted by most cells, including peripheral blood mononuclear cells from SLE patients (preliminary data).
Exomeres demonstrate biophysical properties different from other extracellular vesicles, and contain unique
molecular contents, representing potential source of self-antigens and clinical biomarkers. Importantly,
proteomic analysis of tumor cell-derived exomeres revealed an enrichment of metabolic enzymes, especially in
glycolysis and mTOR signaling. Our preliminary study has shown that uptake of tumor-derived exomeres by
Kupffer cells (resident macrophages in liver) resulted in metabolic alterations in the liver. Therefore, we
hypothesize that circulating exomeres function as pathologic mediators in SLE development and reprogram the
metabolism in target cells. To test this hypothesis, we will employ our expertise in the AF4 technology to
identify and characterize exomeres present in the plasma (Aim 1.1) and secreted by circulating immune cells
(B cells and monocytes) (Aim 1.2) from SLE patients and healthy control subjects. Biophysical properties and
molecular composition (proteins, metabolites and nucleic acids) of these particles will be characterized. We will
investigate the functional roles of exomeres in SLE pathogenesis by examining their impact upon immune cell
activation, IFN production, oxidized mitochondrial DNA extrusion from neutrophils, and plasmacytoid DC
activation (Aim 2.1). Specifically, we will examine whether exomeres from the plasma of SLE patients alternate
the metabolic processes in their target cells (Aim 2.2). This study will provide a novel resource of biomarkers
for SLE patient stratification and disease ac...

## Key facts

- **NIH application ID:** 9906175
- **Project number:** 5U19AI144301-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Haiying Zhang
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $205,431
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906175

## Citation

> US National Institutes of Health, RePORTER application 9906175, Identification and Functional characterization of circulating exomeres in systemic lupus erythematosus (5U19AI144301-02). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/9906175. Licensed CC0.

---

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