Transforming growth factor β1 inhibits expression of NKP30 and NKG2d receptors: Consequences for the NK-mediated killing of dendritic cells

Roberta Castriconi, Claudia Cantoni, Mariella Della Chiesa, Massimo Vitale, Emanuela Marcenaro, Romana Conte, Roberto Biassoni, Cristina Bottino, Lorenzo Moretta, Alessandro Moretta

Research output: Contribution to journalArticle

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 β1 (TGFβ1) down-regulates the surface expression of NKp30 and in part of NKG2D but not that of other triggering receptors such as NKp46. The TGFβ1-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 TGFβ1-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 TGFβ1-producing dendritic cells may acquire resistance to the NK-mediated attack.

Original languageEnglish
Pages (from-to)4120-4125
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number7
DOIs
Publication statusPublished - Apr 1 2003

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ASJC Scopus subject areas

  • General
  • Genetics

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