Glucuronoxylomannan promotes the generation of  antigen-specific T regulatory cell that suppresses  the antigen-specific Th2 response upon activation.
T regulatory cells (Treg) have the capability to suppress the skewed immune response, but the generation of antigen (Ag)-specific Treg for therapeutic purpose is a challenge; the mechanism of Ag-specific Treg activation remains obscure. Here, we report that glucuronoxylomannan (GXM) is capable of promoting the development of human tolerogenic dendritic cells (DC). GXM-pulsed DCs increased the expression of forkhead box P3 (Foxp3) in naïve human CD4(+)CD25(-) T cells via activating Fc gamma receptor IIb and activator protein-1 and promoting the expression of transforming growth factor beta in dendritic cells. Furthermore, the conjugated complex of house dust mite Ag, Dermatophagoides pteronyssinus (Der p) 1, and GXM-pulsed DCs to drive the naïve human CD4(+)CD25(-) T cells to develop into the Der p 1-specific Tregs, which efficiently suppressed the Ag-specific Th2 responses. We conclude that GXM-conjugated specific Ag have the capacity to up-regulate the tolerogenic property of DCs and promote the generation of Ag-specific Tregs; the latter can be activated upon the re-exposure to specific Ag and suppress the skewed Ag-specific T helper (Th)2 responses.
Liu
Tao
T
Allergy Unit, First Hospital, Shanxi Medical University, Taiyuan, China.
Chen
Xiao
X
Brain Body Institute and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Feng
Bai-Sui
BS
Brain Body Institute and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
He
Shao-Heng
SH
Clinical Experimental Center, First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Zhang
Tao-Yuan
TY
Allergy Unit, First Hospital, Shanxi Medical University, Taiyuan, China.
Wang
Bin-Quan
BQ
Allergy Unit, First Hospital, Shanxi Medical University, Taiyuan, China.
Yang
Ping-Chang
PC
Brain Body Institute and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
D000941:Antigens / Q000276:immunology*; D001483:Base Sequence; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers; D006801:Humans; D008213:Lymphocyte Activation; D011134:Polysaccharides / Q000494:pharmacology*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology
D000941:Antigens; D017931:DNA Primers; D011134:Polysaccharides; C027478:glucuronoxylomannan