# Mechanisms of CD49a Expression and Resident Memory T Cell Formation in Skin.

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $416,850

## Abstract

The immune system must defend the host at the most likely sites of pathogen encounter--the epithelial cell
boundaries between barrier organs and the host's environment. Exciting recent data demonstrate that a
population of memory T cells (TRM) resides long-term within peripheral tissues and provides a first line of host
defense from pathogens that cause local infection. However, in some settings, the local persistence of memory
T cells that provide robust response is detrimental. TRM are thought to play a key role in local, recurring
inflammatory skin diseases. This proposal seeks to address significant gaps in our understanding of the
mechanisms that regulate cutaneous TRM in health and disease. Defining mechanisms that control TRM
precursor localization and persistence within skin will be important for optimizing vaccines to provide local
protection as well as therapies to prevent unwanted inflammation. Mechanisms that direct the interstitial
migration, persistence and response of cutaneous TRM will be defined in a normal immune response to HSV
infection and in autoimmune vitiligo. While the local cytokine microenvironment is known to direct TRM
formation, factors that inhibit TRM differentiation/persistence are unknown. This proposal will investigate the
hypothesis that depending on the cytokine microenvironment TRM formation is either promoted or inhibited.
Lastly, although TRM have been identified at sites of cutaneous inflammatory disease, targeting TRM is an
untested therapeutic approach. We will use a mouse model of vitiligo with clinical application to investigate the
novel hypothesis that autoreactive TRM maintain depigmentation, and that depletion of autoreactive TRM will
prevent and/or ameliorate disease. Up-regulating pathways that promote the persistence of T cells in
peripheral tissues is a critical focus of current vaccine design; it may be equally important to create approaches
that reverse these pathways to prevent unwanted TRM accumulation within inflamed tissues.

## Key facts

- **NIH application ID:** 9935006
- **Project number:** 5R01AI121546-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** SHANNON K BROMLEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $416,850
- **Award type:** 5
- **Project period:** 2016-06-23 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9935006

## Citation

> US National Institutes of Health, RePORTER application 9935006, Mechanisms of CD49a Expression and Resident Memory T Cell Formation in Skin. (5R01AI121546-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9935006. Licensed CC0.

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