Toll-like receptor signal is required in maintenance of immune suppressive capacity of regulatory T cells

Abstract

Dysfunction of immune regulatory cells has been recognized in a variety of immune diseases; the underlying mechanism remains to be further investigated. This study aims to investigate the critical role of Toll-like receptor (TLR) signal in the maintenance of function of regulatory T cells (Tregs). In this study, Tregs were isolated from patients with allergic rhinitis (AR) and healthy control (HC) subjects. The role of TLR signal in the maintenance of Treg's function was tested with experiments of cell culture and an AR mouse model. We observed that the immune suppressive function of AR Treg (Tregs isolated from AR patients) was impaired, although the number of peripheral AR Treg was comparable with HC Treg. Expression of transforming growth factor (TGF)-β was lower in AR Tregs than that in HC Tregs that was positively correlated with expression of Mal in Tregs; the latter was lower in AR Tregs as compared to HC Tregs. TGF-β mRNA in Tregs decayed spontaneously in the culture. Activation of Mal counteracted TGF-β decay and maintained the Treg's immune regulatory function. Mal bound Tristetraprolin (TTP) to prevent TTP from inducing TGF-β mRNA decay. Absence of TLR signals resulted in Treg dysfunctional and worsened experimental AR response in a murine model. In conclusion, TLR signal is required in the maintenance of Treg function. Absence of TLR signal may result in Treg dysfunction and immune intolerance.

Keywords: Immune regulation; Immunity; Inflammation; Regulatory T cell; Toll-like receptor.