# Extracellular vesicle-associated MAVS and IFNẞ in Dermatomyositis

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2020 · $201,250

## Abstract

Project Summary/Abstract
 The pathogenesis of dermatomyositis (DM), an autoimmune disease predominantly affecting skin and
muscle, is poorly understood. Increased levels of IFNβ have been reported in DM patients. Levels of IFNβ
correlate with Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity. IFNβ, but not
IFNα, drives the disease activity in DM. Mitochondrial antiviral-signaling protein (MAVS) is an intracellular
adaptor protein linking cytoplasmic RNA sensors, retinoic acid-inducible gene-I (RIG-I), which trigger the
production of IFNβ. The homotypic interaction between the CARDs of MAVS and the CARDs of RIG-I form
protein aggregates and functional clusters on the surface of mitochondria. The MAVS aggregates activate NF-
κB and IRF3, then subsequently resulting in IFNβ production. Peripheral blood mononuclear cells (PBMCs)
from SLE patients contain MAVS in spontaneous aggregation that correlates with the increased levels of IFNβ.
Recent studies indicate that MAVS can also be detected extracellularly in the plasma of lupus patients, and in
the conditioned medium of cultured cells. The extracellular MAVS, isolated with anti-MAVS conjugated beads
from lupus plasma, can be taken up by dendritic cells (DC) and result in IFNβ production. The underlying
mechanisms are unclear. Extracellular vesicles (EVs) harbor bioactive molecules, and mediate intercellular
communications. Studies from our and other groups indicate the importance of EVs in disease pathogenesis,
and that EVs can also serve as a biomarker for monitoring of disease severity. Our preliminary studies showed
that the extracellular MAVS associated with EVs in an aggregated form, and EVs can mediate the delivery of
these MAVS aggregates into the recipient cells for functional activation of the downstream effector NF-kB and
production of IFNβ in myeloid dendritic cells (mDCs). Several studies have reported the increased plasma
levels of EVs in patients with DM. Our preliminary data also showed the existence of MAVS aggregates in the
plasma of DM, and the isolated EVs from plasma of DM patients can activate the downstream effector NF-kB
in mDCs. Therefore, our central hypothesis is that EV-associated extracellular MAVS can functionally
enhance type I IFN production and propagate inflammatory responses, therefore playing an important
role in DM. In Aim 1, we will investigate the cellular mechanisms of EV-associated MAVS in IFNβ induction in
mDCs by using MAVS deficient and wildtype cells. In Aim 2, we will determine the role of EV-associated MAVS
in IFNβ production, and their relationship with the disease activity in patients with DM. Overall, the proposed
studies will investigate the cellular mechanisms of EV-associated extracellular MAVS in IFNβ production, and
the potential involvement of MAVS-positive EVs in autoimmune skin inflammation in DM. This study will
advance our understanding of the disease pathophysiology and provide insights into new therapeutic
strategie...

## Key facts

- **NIH application ID:** 9851815
- **Project number:** 5R21AI144838-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Ming-Lin Liu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $201,250
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851815

## Citation

> US National Institutes of Health, RePORTER application 9851815, Extracellular vesicle-associated MAVS and IFNẞ in Dermatomyositis (5R21AI144838-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851815. Licensed CC0.

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