Inhibitory effect of corneal endothelial cells on IL-17-producing Th17 cells.

Abstract

To determine whether cultured corneal endothelial (CE) cells suppress interleukin 17 (IL-17)-producing effector T cells in vitro. CE cell lines established from a normal mouse were used. Target bystander T cells were established from normal splenic T cells with anti-CD3 antibodies. Production of IL-17 by target T cells was evaluated by ELISA, flow cytometry and quantitative PCR. To abolish the CE-inhibitory function, transforming growth factor β (TGFβ)-small interfering RNA-transfected CE cells or transwell membrane inserts, which block cell-to-cell contact, were used. Cultured CE cells greatly suppressed the activation of bystander target cells (pan-T, CD4 T, CD8 T, and B cells) in vitro, particularly inflammatory cytokine production by CD4 cells. Cultured CE cells significantly suppressed IL-17-producing T cells and fully suppressed polarised T helper 17 (Th17) cell lines that are induced by Th17-associated differentiation factors. However, CE cells failed to suppress Th17 cells if the CE cell lines were pretreated with TGFβ small interfering RNA or if direct contact with T cells was blocked with transwell membrane inserts. CE cells impair the effector functions and activation of IL-17-producing helper T cells in a cell-contact-dependent mechanism. Thus, corneal endothelium may contribute to the maintenance of the privileged immune status in the eye by inducing peripheral immune tolerance.