# Determinants of sex disparities in autoimmune endocrinopathies.

> **NIH NIH U19** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $122,239

## Abstract

PROJECT SUMMARY / ABSTRACT (PILOT PROJECT)
A number of autoimmune endocrinopathies are sex biased, with strong female predisposition For instance,
female:male prevalence ratios have been estimated to be 19:1 for autoimmune thyroiditis. Previous work has
suggested a role for divergent levels of sex hormones as an underlying cause. In particular, increased androgen
signaling drives expression of the transcription factor TCF7, which dampens conversion of CD8+ T cell progenitor
to effector cells. The resultant decrease in the pool of effectors, the cell type mediating direct destruction of
endocrine tissues, protects from endocrine autoimmunity. Our recent data point to an additional role for increased
X chromosome copy number in female sex bias, since deficiency of the X-linked gene UTX also suppresses
progenitor to effector conversion. Thus, we will test the hypothesis that sex differences in human autoimmune
endocrinopathies is driven by both increased X-linked UTX expression and lower androgen levels in females. In
Aim 1, we will determine the role of the X-linked genes promoting progenitor to effector conversion. We will utilize
virally-mediated UTX overexpression to determine the effects of this X-linked gene in effector differentiation.
Additionally, we will query effector differentiation in CD8+ T cells from patients with Klinefelter Syndrome, a
condition in which phenotypic males have an extra X chromosome (47XXY). In Aim 2, we will determine the
effects of androgen and estrogen signaling on TCF7 expression and progenitor to effector conversion.
Understanding mechanisms underlying sex differences is critical for identifying new drug targets and tailoring
therapeutic approaches in a personalized manner for patients with autoimmune endocrinopathies.

## Key facts

- **NIH application ID:** 10845212
- **Project number:** 1U19AI181729-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Maureen A Su
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $122,239
- **Award type:** 1
- **Project period:** 2024-09-10 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10845212

## Citation

> US National Institutes of Health, RePORTER application 10845212, Determinants of sex disparities in autoimmune endocrinopathies. (1U19AI181729-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10845212. Licensed CC0.

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