15 kDa granulysin causes differentiation of monocytes to dendritic cells but lacks cytotoxic activity

Carol Clayberger, Michael W. Finn, Tianhong Wang, Reena Saini, Christine Wilson, Valarie A. Barr, Marianna Sabatino, Luciano Castiello, David Stroncek, Alan M. Krensky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6119-6126
Number of pages8
JournalJournal of Immunology
Volume188
Issue number12
DOIs
StatePublished - Jun 15 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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