# Regulation of dermal gammadelta T cells by microbial pathogens/commensals in health and psoriasis

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2021 · $189,495

## Abstract

Project Summary
 Psoriasis is one of the most common immune-related chronic inflammatory skin disorders. Clinical
observations suggest that streptococcal infection has an intimate relationship in triggering psoriasis onset and
exacerbating chronic psoriasis. Humanized IL-12/IL-23 p40, IL-17A, and IL-17 receptor mAbs have shown
remarkable therapeutic efficacy for the treatment of chronic plaque psoriasis, suggesting IL-23/IL-17 axis plays
important roles in psoriasis pathogenesis. Our previous studies have demonstrated that dermal γδ T cells are
the major IL-17 producers in the skin and are critical in psoriasis pathogenesis. Dermal γδ T cells are
phenotypically and functionally unique. However, it is largely unknown how these cells are critically regulated in
mice and humans, particularly in the context of microbial infection and skin microbial commensal alteration.
 In the proposal, we provided preliminary data suggesting that dermal γδ T cells play critical roles in skin
immune surveillance and inflammation. IL-1β signaling pathway plays a crucial role in regulating dermal γδ T
cell proliferation, IL-17 production, and probably trafficking in mice. Pathogen products stimulated skin cells to
produce IL-1β. In addition, we showed that skin microbiota from psoriatic skin has been substantially altered
compared to that in healthy control skin. Human Vγ9Vδ2 T cells were capable of secreting IL-17 and
significantly decreased in the peripheral blood of psoriatic patients but increased in psoriatic skin lesions and
produced large amounts of IL-17. Based on these preliminary findings, we hypothesize that dysregulated
dermal γδ T cells via IL-1 signaling by pathogen infection or skin microbiota alteration play an essential
role in psoriasis pathogenesis. Three Aims are proposed to address this hypothesis. Aim 1 determines the
role of IL-1 signaling in psoriasis immunopathogenesis. We will test the hypothesis that IL-1 signaling regulates
psoriasis immunopathogenesis through 1) directly activating dermal γδ T cells; 2) stimulating KC to secrete
chemokines which chemoattract more IL-17-producing γδ T cells from periphery into dermis thus amplifying
skin inflammatory cascade; 3) generating memory-like dermal γδ T cells for disease relapse. Aim 2 examines
how skin commensal microorganisms regulate dermal γδ T cell homeostasis in healthy skins and dermal γδ T
cell activation in skin inflammation. Aim 3 determines how human Vγ9 T cells are regulated by pathogen
components or skin microbiota alteration for expansion and IL-17 production. Human skin/SCID mouse
xenograft model will be established to determine the pathogenic roles of human Vγ9 T cells and microbial
infection/commensal alteration in psoriasis pathogenesis. It is believed that this study will provide new insights
into understanding the biology of dermal γδ T cell population and immuno-pathogenesis of psoriasis.

## Key facts

- **NIH application ID:** 10128362
- **Project number:** 5R01AI128818-05
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** JUN YAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $189,495
- **Award type:** 5
- **Project period:** 2017-04-20 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128362

## Citation

> US National Institutes of Health, RePORTER application 10128362, Regulation of dermal gammadelta T cells by microbial pathogens/commensals in health and psoriasis (5R01AI128818-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10128362. Licensed CC0.

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