Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells

Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4120-5. doi: 10.1073/pnas.0730640100. Epub 2003 Mar 19.

Abstract

The surface density of the triggering receptors responsible for the natural killer (NK)-mediated cytotoxicity is crucial for the ability of NK cells to kill susceptible target cells. In this study, we show that transforming growth factor beta1 (TGFbeta1) down-regulates the surface expression of NKp30 and in part of NKG2D but not that of other triggering receptors such as NKp46. The TGFbeta1-mediated inhibition of NKp30 surface expression reflects gene regulation at the transcriptional level. NKp30 has been shown to represent the major receptor involved in the NK-mediated killing of dendritic cells. Accordingly, the TGFbeta1-dependent down-regulation of NKp30 expression profoundly inhibited the NK-mediated killing of dendritic cells. On the contrary, killing of different NK-susceptible tumor cell lines was variably affected, reflecting the differential usage of NKp30 and/or NKG2D in the lysis of such tumors. Our present data suggest a possible mechanism by which TGFbeta1-producing dendritic cells may acquire resistance to the NK-mediated attack.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / analysis
  • Cell Survival / drug effects
  • Cell Survival / immunology*
  • Cells, Cultured
  • Cytotoxicity, Immunologic / drug effects*
  • DNA Primers
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Flow Cytometry
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology*
  • Humans
  • Immunoglobulins / genetics
  • Interleukin-2 / genetics
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • NK Cell Lectin-Like Receptor Subfamily K
  • Natural Cytotoxicity Triggering Receptor 3
  • Receptors, Immunologic / genetics*
  • Receptors, Natural Killer Cell
  • Recombinant Proteins / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta1

Substances

  • Antigens, CD
  • DNA Primers
  • Immunoglobulins
  • Interleukin-2
  • KLRK1 protein, human
  • NCR3 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • Natural Cytotoxicity Triggering Receptor 3
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Recombinant Proteins
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1