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Lymphocyte Isolation from Human Skin for Phenotypic Analysis and Ex Vivo Cell Culture
Published on: April 8, 2016
CD8+ T cell granzyme B activates keratinocyte endogenous IL-18
Tomoko Akeda1, Keiichi Yamanaka, Kenshiro Tsuda
1Department of Dermatology, Mie University, Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
Archives of Dermatological Research
|July 4, 2013
Summary
Cytotoxic T lymphocytes (CTLs) release granzyme B (GrB), which activates interleukin-18 (IL-18) in skin cells. This GrB also promotes apoptosis, contributing to inflammatory skin diseases.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Interleukin-18 (IL-18) is a pro-inflammatory cytokine crucial for Th1/Th2 immune responses.
- IL-18 requires processing from its inactive precursor (proIL-18) to become active.
- Granzyme B (GrB), released by cytotoxic T lymphocytes (CTLs) and NK cells, is known to cleave proIL-18.
Purpose of the Study:
- To investigate IL-18 activation during direct CTL-keratinocyte interactions.
- To determine the role of CTL-derived Granzyme B (GrB) in IL-18 processing within keratinocytes.
- To elucidate the dual function of GrB in skin inflammatory conditions.
Main Methods:
- Co-culture of Granzyme B (GrB)-positive, caspase-1-negative CD8+ T cells with interferon-γ-treated HaCaT keratinocyte cell line.
- Analysis of GrB and caspase-1 expression in HaCaT cells via flow cytometry and PCR.
- Quantification of mature IL-18 levels in co-culture supernatant using ELISA.
Main Results:
- Co-culture led to increased cytoplasmic GrB in HaCaT cells, despite limited endogenous GrB mRNA.
- Concentrations of mature IL-18 significantly increased in the co-culture supernatant.
- Evidence suggests CTL-derived GrB directly processes proIL-18 in keratinocytes.
Conclusions:
- Cytotoxic T lymphocyte (CTL)-derived Granzyme B (GrB) acts as an IL-18 converting enzyme in keratinocytes.
- GrB also functions as a pro-apoptotic factor, contributing to epidermal cell death in skin inflammation.
- This study reveals a novel mechanism of IL-18 activation and its dual role in inflammatory skin diseases.
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