# Lymphocyte function in inflammatory disorders of human endometrium and decidua

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $626,151

## Abstract

Endometriosis and polycystic ovary syndrome (PCOS) are major causes of female subfertility and infertility. Each
is accompanied by chronic endometrial inflammation triggered and perpetuated by uncertain mechanisms.
Potential roles for immune cells, specifically T and B lymphocytes, in endometrial inflammation are largely
unexplored despite their being key orchestrators and mediators of tissue inflammation in many other non-uterine
contexts. Furthermore, the antigen specificities of endometrial T and B cells are not well described, and whether
self-antigen specific clones contribute to disorders with poor reproductive outcomes is unclear, despite evidence
that endometriosis, in particular, may have an autoimmune component. These knowledge gaps represent major
opportunities for improving reproductive outcomes for infertile patients with endometriosis and PCOS. Moreover,
these disorders represent ideal models for investigating how immune dysregulation in the endometrium may
contribute to infertility and subfertility more broadly. Accordingly, the goal of this project is to determine how T
and B cells contribute to the pathogenesis of endometrial inflammation and, by extension, decidual inflammation,
relevant to implantation failure and poor pregnancy outcomes. Herein, we propose to deeply characterize the
frequencies, transcriptomes, proteomes, TCR/BCR repertoires, and antigen specificities of endometrial and
decidual T and B cells across the menstrual cycle and in early pregnancy, respectively, in the context of healthy
women (Aim 1) and those with endometriosis and PCOS (Aim 2). Particular emphasis will be placed on regulatory
lymphocytes, which include conventional CD4+ regulatory T cells (Tregs), and cells from the CD8+ T cell and B
cell lineages, since these cells are likely critical for ensuring a controlled inflammatory microenvironment optimal
for implantation and successful pregnancy. Since the differentiation and function of these cells can be locally
influenced by non-immune endometrial and decidual cells, such as stromal fibroblasts, Aim 3 will define the role
of such cells in supporting suppressive lymphocyte differentiation and identify the key regulators involved in
these processes. The proposal will also determine how endometriosis and PCOS alter the phenotypes of the NK
cell lineage of lymphocytes, given the contribution of NK cells to important developmental events of early
pregnancy. The Aims will be accomplished using archived and prospectively collected endometrial/decidual
specimens from a total of 150 well-characterized subjects. Our central hypothesis is that different lymphocyte
subsets with diverse roles in immunoregulation and microbial defense work together in a coordinated fashion to
establish and maintain the appropriate endometrial and decidual environment for pregnancy success, and that
these cells are altered and derailed by inflammatory disorders associated with poor reproductive outcomes.
Completion of this study w...

## Key facts

- **NIH application ID:** 10673395
- **Project number:** 1P50HD112034-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Heather G Huddleston
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $626,151
- **Award type:** 1
- **Project period:** 2023-08-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10673395

## Citation

> US National Institutes of Health, RePORTER application 10673395, Lymphocyte function in inflammatory disorders of human endometrium and decidua (1P50HD112034-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10673395. Licensed CC0.

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