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Updated: May 22, 2026
Characterization of Human Monocyte-derived Dendritic Cells by Imaging Flow Cytometry: A Comparison between Two Monocyte Isolation Protocols
Published on: October 18, 2016
15 kDa granulysin causes differentiation of monocytes to dendritic cells but lacks cytotoxic activity
Carol Clayberger1, Michael W Finn, Tianhong Wang
1Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
Granulysin is expressed as two isoforms by human cytotoxic cells: a single mRNA gives rise to 15 kDa granulysin, a portion of which is cleaved to a 9 kDa protein. Studies with recombinant 9 kDa granulysin have demonstrated its cytolytic and proinflammatory properties, but much less is known about the biologic function of the 15 kDa isoform. In this study, we show that the subcellular localization and functions of 9 and 15 kDa granulysin are largely distinct. Nine kilodalton granulysin is confined to cytolytic granules that are directionally released following target cell recognition. In contrast, 15 kDa granulysin is located in distinct granules that lack perforin and granzyme B and that are released by activated cytolytic cells. Although recombinant 9 kDa granulysin is cytolytic against a variety of tumors and microbes, recombinant 15 kDa granulysin is not. The 15 kDa isoform is a potent inducer of monocytic differentiation to dendritic cells, but the 9 kDa isoform is not. In vivo, mice expressing granulysin show markedly improved antitumor responses, with increased numbers of activated dendritic cells and cytokine-producing T cells. Thus, the distinct functions of granulysin isoforms have major implications for diagnosis and potential new therapies for human disease.
Insights
Human cytotoxic cells express two granulysin isoforms with distinct functions. The 9 kDa isoform is cytolytic, while the 15 kDa isoform promotes dendritic cell differentiation, impacting antitumor responses and disease therapies.
Area of Science:
- Immunology
- Cell Biology
Background:
- Granulysin, a protein expressed by cytotoxic cells, exists in two isoforms: 9 kDa and 15 kDa.
- While the 9 kDa isoform's cytolytic and proinflammatory functions are known, the 15 kDa isoform's role is less understood.
Purpose of the Study:
- To elucidate the distinct subcellular localization and biological functions of the 9 kDa and 15 kDa granulysin isoforms.
- To investigate the therapeutic potential of granulysin isoforms in antitumor responses.
Main Methods:
- Subcellular localization studies of granulysin isoforms.
- Functional assays using recombinant granulysin isoforms.
- In vivo studies in mice to assess antitumor responses.
Main Results:
- The 9 kDa granulysin is localized in cytolytic granules and exhibits cytolytic activity against tumors and microbes.
- The 15 kDa granulysin resides in distinct granules and induces monocytic differentiation into dendritic cells.
- Mice expressing granulysin demonstrated enhanced antitumor responses, with increased dendritic cells and T cells.
Conclusions:
- The 9 kDa and 15 kDa granulysin isoforms possess largely distinct functions and subcellular localizations.
- The 15 kDa isoform's role in dendritic cell differentiation suggests potential as a therapeutic target for cancer.
- Understanding granulysin isoform functions has significant implications for disease diagnosis and novel therapeutic strategies.
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