Frontiers in Immunology (Jun 2024)
Granzyme K mediates IL-23-dependent inflammation and keratinocyte proliferation in psoriasis
- Katlyn C. Richardson,
- Katlyn C. Richardson,
- Katlyn C. Richardson,
- Alexandre Aubert,
- Alexandre Aubert,
- Alexandre Aubert,
- Christopher T. Turner,
- Christopher T. Turner,
- Christopher T. Turner,
- Layla Nabai,
- Layla Nabai,
- Layla Nabai,
- Sho Hiroyasu,
- Sho Hiroyasu,
- Sho Hiroyasu,
- Megan A. Pawluk,
- Megan A. Pawluk,
- Megan A. Pawluk,
- Rachel A. Cederberg,
- Rachel A. Cederberg,
- Hongyan Zhao,
- Hongyan Zhao,
- Hongyan Zhao,
- Karen Jung,
- Karen Jung,
- Karen Jung,
- Angela Burleigh,
- Richard I. Crawford,
- Richard I. Crawford,
- David J. Granville,
- David J. Granville,
- David J. Granville
Affiliations
- Katlyn C. Richardson
- International Collaboration on Repair Discoveries (ICORD) Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- Katlyn C. Richardson
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Katlyn C. Richardson
- British Columbia Professional Firefighters’ Burn and Wound Healing Group, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- Alexandre Aubert
- International Collaboration on Repair Discoveries (ICORD) Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- Alexandre Aubert
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Alexandre Aubert
- British Columbia Professional Firefighters’ Burn and Wound Healing Group, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- Christopher T. Turner
- International Collaboration on Repair Discoveries (ICORD) Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- Christopher T. Turner
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Christopher T. Turner
- British Columbia Professional Firefighters’ Burn and Wound Healing Group, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- Layla Nabai
- International Collaboration on Repair Discoveries (ICORD) Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- Layla Nabai
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Layla Nabai
- British Columbia Professional Firefighters’ Burn and Wound Healing Group, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- Sho Hiroyasu
- International Collaboration on Repair Discoveries (ICORD) Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- Sho Hiroyasu
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Sho Hiroyasu
- British Columbia Professional Firefighters’ Burn and Wound Healing Group, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- Megan A. Pawluk
- International Collaboration on Repair Discoveries (ICORD) Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- Megan A. Pawluk
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Megan A. Pawluk
- British Columbia Professional Firefighters’ Burn and Wound Healing Group, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- Rachel A. Cederberg
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Rachel A. Cederberg
- Integrative Oncology Department, British Columbia (BC) Cancer Research Centre, Vancouver, BC, Canada
- Hongyan Zhao
- International Collaboration on Repair Discoveries (ICORD) Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- Hongyan Zhao
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Hongyan Zhao
- British Columbia Professional Firefighters’ Burn and Wound Healing Group, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- Karen Jung
- International Collaboration on Repair Discoveries (ICORD) Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- Karen Jung
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Karen Jung
- British Columbia Professional Firefighters’ Burn and Wound Healing Group, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- Angela Burleigh
- Department of Dermatology and Skin Sciences, University of British Columbia, Vancouver, BC, Canada
- Richard I. Crawford
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Richard I. Crawford
- Department of Dermatology and Skin Sciences, University of British Columbia, Vancouver, BC, Canada
- David J. Granville
- International Collaboration on Repair Discoveries (ICORD) Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- David J. Granville
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
- David J. Granville
- British Columbia Professional Firefighters’ Burn and Wound Healing Group, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada
- DOI
- https://doi.org/10.3389/fimmu.2024.1398120
- Journal volume & issue
-
Vol. 15
Abstract
Psoriasis is an inflammatory disease with systemic manifestations that most commonly presents as itchy, erythematous, scaly plaques on extensor surfaces. Activation of the IL-23/IL-17 pro-inflammatory signaling pathway is a hallmark of psoriasis and its inhibition is key to clinical management. Granzyme K (GzmK) is an immune cell-secreted serine protease elevated in inflammatory and proliferative skin conditions. In the present study, human psoriasis lesions exhibited elevated GzmK levels compared to non-lesional psoriasis and healthy control skin. In an established murine model of imiquimod (IMQ)-induced psoriasis, genetic loss of GzmK significantly reduced disease severity, as determined by delayed plaque formation, decreased erythema and desquamation, reduced epidermal thickness, and inflammatory infiltrate. Molecular characterization in vitro revealed that GzmK contributed to macrophage secretion of IL-23 as well as PAR-1-dependent keratinocyte proliferation. These findings demonstrate that GzmK enhances IL-23-driven inflammation as well as keratinocyte proliferation to exacerbate psoriasis severity.
Keywords
