Effect of Shear force on immunosuppressive property of human periodontal ligament cells

Abstract

The immunomodulatory property is to regulate immune cell function. IDO and TGF-β1 inhibited T cell proliferation and induced regulatory T (Treg) cells differentiation. However, this property must be activated by inflammation. Recently, mechanical forces have also activated this property. Hence, this study investigated effect of shear stress on immunosuppressive property of hPDL cells. Cells were subjected to shear stress then expression of IDO, TGF-β1, IFN-gamma and COX2 mRNA and protein was examined by qRT-PCR, ELISA, and IDO activity. Conditioned media derived shear stress were treated with CD4+ T cells. The proliferative T cell effect was determined using resazurin. The FOXP3, IL-10, and CD4+CD25hiCD127lo/- were tested using qRT-PCR and flow cytometry. Our result showed the IDO-dependent kynurenine and TGF-β1 were increased under shear stress. The addition of ERK inhibitor, or cycloheximide inhibited shear stress-induced kynurenine. Shear stress-derived conditioned medium (SS-CM) inhibited T cell proliferation. Also, SS-CM enhanced FOXP3 and IL-10 mRNA and increased Treg cells. In conclusion, shear stress enhances immunosuppressive property of hPDL cells, thereby inhibit T cells proliferation and promote Treg cell differentiation. The potential of shear force in regulating immunosuppressive property may possibly be applied in periodontitis to regulate inflammation and trigger tissue regeneration.