# Effect of Th2-type microenvironment on CD8 TRM-mediated protection from infection

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $607,611

## Abstract

Project Summary Abstract
Individuals suffering from atopic dermatitis have increased risk for serious recurrent and disseminated viral
infections, but the cause is unclear. Defense against local infections relies on tissue resident memory CD8+ T
cells (TRM) that deliver rapid defense against invading pathogens. We hypothesize that impairment of CD8+ TRM
contributes to severe infection in patients with atopic dermatitis. Our preliminary data demonstrate that IL-4
counters TGF-b-induced expression of CD8+ TRM receptors that are required for persistence within peripheral
tissues. In parallel, in vivo studies reveal that exposure of CD8+ T cells to IL-4 decreases their accumulation
within inflamed skin. Based on these preliminary data, we hypothesize that IL-4 prevents TGF-b-mediated
signaling and/or changes the chromatin landscape surrounding TGF-b target genes in CD8+ T cells, resulting
in an altered CD8+ T cell phenotype. We predict that these phenotypic changes impede the long-term
persistence of cutaneous CD8+ TRM and impair TRM-mediated defense against local viral infection. We will test
these hypotheses by i) using mouse models of allergic eczema to analyze the impact of local Th2-type
inflammation on CD8+ TRM persistence and protection from HSV infection ii) analyzing the effect of Th2
cytokines on the phenotype and function of human CD8+ TRM, and iii) investigating the impact of IL-4 on TGF-
bR signaling and the chromatin landscape of CD8+ T cells.

## Key facts

- **NIH application ID:** 10830990
- **Project number:** 5R01AI163517-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** SHANNON K BROMLEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $607,611
- **Award type:** 5
- **Project period:** 2022-05-19 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10830990

## Citation

> US National Institutes of Health, RePORTER application 10830990, Effect of Th2-type microenvironment on CD8 TRM-mediated protection from infection (5R01AI163517-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10830990. Licensed CC0.

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