# Commensal-specific T cell function in skin wound repair

> **NIH NIH R01** · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2022 · $587,319

## Abstract

PROJECT SUMMARY
Our understanding of immunity largely stems from models of infection with pathogenic microbes. However, the
vast majority of microbial-immune encounters occur as a symbiotic relationship with the commensal microbiota.
Recently, the contribution of commensal-specific T cells to host physiology has received significant attention.
These commensal-specific responses not only control microbiota containment but also promote antimicrobial
defenses via their action on both innate and epithelial cells. Local tuning of keratinocytes by commensal-specific
T cells also contributes to tissue repair following skin injury. Conversely, aberrant immunity to commensal
microbes has been proposed to underlie pathologies of barrier tissues, including atopic dermatitis and
inflammatory bowel disease. A better understanding of the properties and functions of commensal-specific T cell
responses is therefore fundamental to studies of tissue immunity in health and disease. Our long-term goal is to
better understand how commensal-specific T cell responses contribute to barrier tissue homeostasis, and the
objective in this application is to investigate the mechanisms regulating cytokine production during skin injury
and wound repair. Our rationale for the proposed work is that uncovering these mechanisms has the potential to
translate into new therapeutic approaches. Our central hypothesis is that commensal-specific T cells are
sentinels of the skin tissue and contribute to wound repair through rapid production of type-2 cytokines in
response to tissue injury. In this proposal, we will focus on two mechanisms, the post-transcriptional regulation
of IL-5 and IL-13 cytokine production by commensal-specific T through RNA-binding proteins and induction of
the integrated stress response. Based on strong preliminary data, we will test three specific aims: (1) Understand
the key proximal and distal IL-18R-signaling pathways that trigger poised type-2 immunity in commensal-specific
CD8+ T cells. We have recently found that IL-18 acting directly on CD8+ T cells can trigger rapid production of
IL-5 and IL-13. We will test the hypothesis that pathways unique to IL-18R, but not other IL-1R family members
triggers poised type-2 immunity in commensal-specific CD8+ T cells. (2) Determine the role of Untranslated
regions (UTR) of Il5 and Il13 mRNA in poised type-2 immunity in commensal-specific CD8+ T cells. We have
identified multiple RNA-binding protein motifs in the UTR of Il5 and Il13 mRNA. We will test the contribution of
these regulatory elements to poised type-2 immunity in commensal-specific CD8+ T cells. (3) Understand the
contribution of the integrated stress response to post-transcriptional regulation of Il5 and Il13 mRNA in
commensal-specific CD8+ T cells and the contribution to wound repair. Our approach is innovative as it
investigates new mechanisms of immunity unique to commensal-specific T cell responses. The proposed work
is significant because it will est...

## Key facts

- **NIH application ID:** 10337339
- **Project number:** 5R01AI158624-02
- **Recipient organization:** BENAROYA RESEARCH INST AT VIRGINIA MASON
- **Principal Investigator:** Oliver James Harrison
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $587,319
- **Award type:** 5
- **Project period:** 2021-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337339

## Citation

> US National Institutes of Health, RePORTER application 10337339, Commensal-specific T cell function in skin wound repair (5R01AI158624-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10337339. Licensed CC0.

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