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

Abstract

Transforming growth factor-β (TGF-β) 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‑β modulated NK cell function, thereby promoting recovery from renal IRI. Human renal proximal tubular epithelial cells (HK‑2) treated with TGF‑β exhibited increased surface and intracellular expression of the NK group2 memberD (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‑β treatment evidently increased the amount of soluble MICA released into the culture supernatant from HK‑2 cells. Taken together, these findings suggest that TGF‑β‑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.