# Role of the gender biased transcription factor VGLL3 in promoting autoimmune responses in SLE

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $400,179

## Abstract

PROJECT SUMMARY
 Autoimmune diseases feature a dysfunction of the immune system in which the body attacks its own tissues.
By NIH estimations, autoimmune diseases affect 7.5% of the U.S. population, and are among the leading
causes of death and disability. A striking feature of many autoimmune diseases is their increased prevalence
in females, and overall it is estimated that 78% of individuals affected are women. Understanding the cause of
female-biased susceptibility to autoimmune diseases is fundamental to the development of preventative
measures in high-risk populations, and may lead to novel therapeutic approaches for individuals with
established disease.
 Through genome-wide transcriptomic analyses we have identified a female-biased molecular signature
linked to extensive sex-dependent, co-expression networks and associated with autoimmune disease
susceptibility. This signature was independent of biological age and sex-hormone regulation, and regulated by
the transcription factor VGLL3, which had a prominent female biased expression. On a genome-wide level,
VGLL3 target genes were strongly associated with multiple autoimmune diseases including lupus and
scleroderma, and had a prominent transcriptomic overlap with immune processes including cutaneous lupus,
suggesting that VGLL3 is tightly integrated with inflammatory responses in autoimmunity, and an upstream
regulator of autoimmune processes.
The central hypothesis of our proposal, based on these findings, is that VGLL3 is an epigenetically regulated
transcription factor that has critical roles in promoting autoimmune specific inflammatory responses. This
proposal has the potential to significantly advance the field of autoimmune research by increasing our
understanding of a novel sex hormone-independent inflammatory pathway in gender biased autoimmunity,
identify upstream regulators of this pathway, and determine the mechanisms by which VGLL3 mediates
autoimmune responses. SLE will be used as the model disease for study given the strong female bias in lupus
and easy access to patient samples through our clinics and co-investigators. With the successful conclusion of
the work proposed, we will have taken major strides towards understanding the involvement of VGLL3 in
promoting autoimmune responses and disease activity in SLE. In addition, we will provide a solid foundation
towards development of novel preventive and therapeutic measures that may have major implications against
a wide range of autoimmune diseases.

## Key facts

- **NIH application ID:** 9869805
- **Project number:** 5R01AI130025-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Johann Eli Gudjonsson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $400,179
- **Award type:** 5
- **Project period:** 2017-03-06 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9869805

## Citation

> US National Institutes of Health, RePORTER application 9869805, Role of the gender biased transcription factor VGLL3 in promoting autoimmune responses in SLE (5R01AI130025-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9869805. Licensed CC0.

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