Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells.
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.
Castriconi
Roberta
R
Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Via L.B. Alberti 1, 16132 Genoa, Italy.
Cantoni
Claudia
C
Della Chiesa
Mariella
M
Vitale
Massimo
M
Marcenaro
Emanuela
E
Conte
Romana
R
Biassoni
Roberto
R
Bottino
Cristina
C
Moretta
Lorenzo
L
Moretta
Alessandro
A
D015703:Antigens, CD / Q000032:analysis; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D017931:DNA Primers; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055628:Natural Cytotoxicity Triggering Receptor 3; D011971:Receptors, Immunologic / Q000235:genetics*; D055607:Receptors, Natural Killer Cell; D011994:Recombinant Proteins / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D015703:Antigens, CD; D017931:DNA Primers; D007136:Immunoglobulins; D007376:Interleukin-2; C527085:KLRK1 protein, human; C431710:NCR3 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055628:Natural Cytotoxicity Triggering Receptor 3; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1