IL-15 alters expression and function of the chemokine receptor CX3CR1 in human NK cells

Joan M. Sechler, Jana Barlic, Jean-Charles B. Grivel, Philip M. Murphy

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The chemokine receptor CX3CR1 is thought to regulate inflammation in part by modulating NK cell adhesion, migration, and killing in response to its ligand CX3CL1 (fractalkine). Recent reports indicate that IL-15, which is essential for development and survival of NK cells, may negatively regulate CX3CR1 expression, however, the effects of the cytokine on human NK cell CX3CR1 expression and function have not been fully delineated. Here, we demonstrate that short term culture in IL-15 decreases surface expression of CX3CR1 on cultured CD56 + cells from human blood resulting in diminished chemotaxis and calcium flux in response to CX3CL1. Cells cultured long term in IL-15 (more than five days) completely lost surface expression as well as mRNA and protein for CX3CR1. The effect was specific since mRNA for CCR5 was increased and mRNA for CXCR4 was unchanged in these cells by IL-15. Thus, exogenous IL-15 is a negative regulator of CX3CR1 expression and function in human CD56 + NK cells. The data imply that the use of IL-15 alone to expand NK cells ex vivo for immunotherapy may produce cells impaired in their ability to traffic to sites of inflammation.

Original languageEnglish
Pages (from-to)99-108
Number of pages10
JournalCellular Immunology
Volume230
Issue number2
DOIs
Publication statusPublished - Aug 2004
Externally publishedYes

Fingerprint

Interleukin-15
Chemokine Receptors
Natural Killer Cells
Messenger RNA
Cultured Cells
Chemokine CX3CL1
Inflammation
Aptitude
Chemotaxis
Cell Adhesion
Immunotherapy
Cell Movement
Cytokines
Ligands
Calcium
Proteins

Keywords

  • Chemokine
  • CX3CR1
  • Cytokine
  • Fractalkine
  • Human NK cell
  • IL-15

ASJC Scopus subject areas

  • Immunology

Cite this

IL-15 alters expression and function of the chemokine receptor CX3CR1 in human NK cells. / Sechler, Joan M.; Barlic, Jana; Grivel, Jean-Charles B.; Murphy, Philip M.

In: Cellular Immunology, Vol. 230, No. 2, 08.2004, p. 99-108.

Research output: Contribution to journalArticle

Sechler, Joan M. ; Barlic, Jana ; Grivel, Jean-Charles B. ; Murphy, Philip M. / IL-15 alters expression and function of the chemokine receptor CX3CR1 in human NK cells. In: Cellular Immunology. 2004 ; Vol. 230, No. 2. pp. 99-108.
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