# Regulation of cutaneous immunity and tissue-repair by a specialized population of CD4+ T cells

> **NIH NIH R01** · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2020 · $485,684

## Abstract

Project Summary
Consistent with its functions in maintaining barrier integrity and preventing infection, the skin is home to a
number of specialized T cell populations that not only combat infection but also work in concert to help
maintain normal tissue homeostasis and promote wound repair. However, despite significant advances in
understanding cutaneous immunity, the specific functions of different populations of cutaneous T cells, their
roles in maintaining normal skin homeostasis, and contributions to inflammatory diseases of the skin remain
poorly understood. In this respect, reliance on animal models can be problematic due to fundamental
structural differences in the skin in humans vs. mice, and a lack of direct correspondence between cutaneous
T cell populations in these species. Additionally, although skin-tropic T cells can be readily identified in
peripheral blood based on their expression of the cutaneous lymphocyte antigen (CLA), the developmental and
functional relationship of these cells in the blood with the different populations of T cells in the skin is still poorly
understood.
We have identified a novel population of CLA+CD4+ T cells in the peripheral blood of healthy subjects that
expresses the CD103 integrin and produces the novel cytokine combination of IL-22, GM-CSF and IL-13 upon
activation (CD103+CLAhi cells). Interestingly, this cytokine combination is also produced by phenotypically
similar epidermal CD103 CLA CD69 TRM in the skin itself. Based on the ability of IL-22 to promote
 + hi +
keratinocyte proliferation, migration and production of antimicrobial peptides, and GM-CSF and IL-13 to act on
fibroblasts, and to mediate the differentiation of monocytes and macrophages into `alternatively activated' cells
that promote tissue repair, we hypothesize CD103+CLAhi T cells in the blood represent a recirculating
fraction of CD103+CLAhi TRM, and that these cells help coordinate the host-protective and wound
healing responses following tissue damage in the skin. As such, these cells have the potential to be
manipulated therapeutically to promote sterile wound healing and to optimize the development and function of
engineered tissue grafts.  In this proposal, we will use in vitro analyses and innovative humanized mouse
models to test these hypotheses, assessing the developmental origins and trafficking behavior of CD103+CLAhi
cells and determining their function during cutaneous tissue-repair responses.

## Key facts

- **NIH application ID:** 9926223
- **Project number:** 5R01AI127726-04
- **Recipient organization:** BENAROYA RESEARCH INST AT VIRGINIA MASON
- **Principal Investigator:** Daniel J Campbell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $485,684
- **Award type:** 5
- **Project period:** 2017-06-20 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9926223

## Citation

> US National Institutes of Health, RePORTER application 9926223, Regulation of cutaneous immunity and tissue-repair by a specialized population of CD4+ T cells (5R01AI127726-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9926223. Licensed CC0.

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