TLR5 Signaling Enhances the Proliferation of Human Allogeneic CD40-Activated B Cell Induced CD4hiCD25 Regulatory T CellsReport as inadecuate




TLR5 Signaling Enhances the Proliferation of Human Allogeneic CD40-Activated B Cell Induced CD4hiCD25 Regulatory T Cells - Download this document for free, or read online. Document in PDF available to download.

Although diverse functions of different toll-like receptors TLR on human natural regulatory T cells have been demonstrated recently, the role of TLR-related signals on human induced regulatory T cells remain elusive. Previously our group developed an ex vivo high-efficient system in generating human alloantigen-specific CD4hiCD25+ regulatory T cells from naïve CD4+CD25− T cells using allogeneic CD40-activated B cells as stimulators. In this study, we investigated the role of TLR5-related signals on the generation and function of these novel CD4hiCD25+ regulatory T cells. It was found that induced CD4hiCD25+ regulatory T cells expressed an up-regulated level of TLR5 compared to their precursors. The blockade of TLR5 using anti-TLR5 antibodies during the co-culture decreased CD4hiCD25+ regulatory T cells proliferation by induction of S phase arrest. The S phase arrest was associated with reduced ERK1-2 phosphorylation. However, TLR5 blockade did not decrease the CTLA-4, GITR and FOXP3 expressions, and the suppressive function of CD4hiCD25+ regulatory T cells. In conclusion, we discovered a novel function of TLR5-related signaling in enhancing the proliferation of CD4hiCD25+ regulatory T cells by promoting S phase progress but not involved in the suppressive function of human CD40-activated B cell-induced CD4hiCD25+ regulatory T cells, suggesting a novel role of TLR5-related signals in the generation of induced regulatory T cells.



Author: Ping-Lung Chan, Jian Zheng, Yinping Liu, Kwok-Tai Lam, Zheng Xiang, Huawei Mao, Yuan Liu, Gang Qin, Yu-Lung Lau, Wenwei Tu

Source: http://plos.srce.hr/



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