# Influence of sex-steroid and microbiome on female genital resident memory T cell development

> **NIH NIH P20** · WOMEN AND INFANTS HOSPITAL-RHODE ISLAND · 2020 · $157,945

## Abstract

The mucosal surface of female reproductive tract (FRT) is a common site of pathogen replication. Many of 
these pathogens establish sexually transmitted infections (STls) that are a hidden epidemic of significant 
health and economic concern worldwide. Many STls, including HIV and Herpes simplex virus (HSV), lack 
curative therapies and would immensely benefit from preventive vaccination. Anti-HIV and HSV-2 vaccine trials 
that are solely focused on generating neutralizing antibodies have so far failed to provide significant protective 
benefits. There is a growing realization that an effective mucosal vaccine regimen should elicit both antibodies 
and T cells. Resident memory T cells (TRM), the dominant T cell population in the genital mucosa, represent a 
primary defense mechanism against intracellular pathogens. Contrary to circulating memory T cells, TRM 
establish permanent residence in their tissue of origin and do not routinely circulate via blood and lymph. 
Reductionist experiments in rodent and non-human primate models suggest a strong protective role of 
mucosal TRM located near the site of infection. Hence, establishing an abundant number of highly functional 
CD8 TRM in the FRT to mediate rapid pathogen clearance is a key long-term goal of many vaccination 
programs. However, achieving sufficient quantity and quality of mucosal TRM hinges on a detailed 
understanding of the differentiation and maintenance requirement of these cells. It has been recently 
recognized that the local environmental milieu is a significant contributor to TRM differentiation program and 
their long-term maintenance. Our preliminary data indicate a critical role of estrogen in impacting FRT TRM 
formation. The overall objective of this proposal is to interrogate the contributions of sex-hormone and the local 
microbiome in shaping the FRT TRM compartment. Under first aim, we will utilize reductionist mouse model based 
approaches to investigate the role CD8 T cell intrinsic estrogen signaling in establishment of FRT TRM. 
In the second aim, we will use germfree mice and microbiome depletion approaches to examine the influence 
of local microbiome on TRM formation and function. Identification of local factors that contribute to TRM 
differentiation and function will aid in developing methods to generate a robust T cell response in the 
reproductive mucosa.

## Key facts

- **NIH application ID:** 10328294
- **Project number:** 5P20GM121298-04
- **Recipient organization:** WOMEN AND INFANTS HOSPITAL-RHODE ISLAND
- **Principal Investigator:** Lalit K Beura
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $157,945
- **Award type:** 5
- **Project period:** 2020-12-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328294

## Citation

> US National Institutes of Health, RePORTER application 10328294, Influence of sex-steroid and microbiome on female genital resident memory T cell development (5P20GM121298-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10328294. Licensed CC0.

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