Transforming growth factor β1 inhibits expression of NKp30 and NKG2D receptors: Consequences for the NK-mediated killing of dendritic cells

TLDR

NK cell cytotoxicity depends on the surface density of triggering receptors, with NKp30 identified as the key receptor for killing dendritic cells. The study investigates whether TGFβ1 down‑regulates NKp30 and partially NKG2D surface expression on NK cells. TGFβ1 transcriptionally suppresses NKp30, markedly reducing NK cell killing of dendritic cells while only variably affecting tumor cell lysis, implying that TGFβ1‑producing dendritic cells may evade NK attack.

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.