Transforming growth factor-β1 regulates human renal proximal tubular epithelial cell susceptibility to natural killer cells via modulation of the NKG2D ligands

Transforming growth factor-beta (TGF-beta) has a significant role in the response to injury and tissue repair, and it has been detected in various cell types. However, the mechanism by which it regulates the response to ischemia-reperfusion injury (IRI) and manipulates natural killer (NK) cells is not well understood. In the present study, TGF-beta modulated NK cell function, thereby promoting recovery from renal IRI. Human renal proximal tubular epithelial cells (HK-2) treated with TGF-beta exhibited increased surface and intracellular expression of the NK group 2 member D (NKG2D) ligand MICA. This increased surface expression of MICA inhibited NK cell cytotoxicity to the HK-2 cells. In addition, an enzyme-linked immunosorbent assay revealed that TGF-beta treatment evidently increased the amount of soluble MICA released into the culture supernatant from HK-2 cells. Taken together, these findings suggest that TGF-beta-induced release of soluble MICA leads to downregulation of NKG2D, thereby preventing NK cell-mediated cytotoxicity toward renal proximal tubular epithelial cells in renal IRI, which in turn improves the survival of these cells.