Staphylococcal enterotoxin B increases TIM4 expression in human dendritic cells that drives naïve CD4 T cells to differentiate into Th2 cells.
Aberrant T helper (Th)2 polarization plays a critical role in the pathogenesis of allergic disorders; the etiology remains unclear. Dendritic cells (DCs) express T cell immunoglobulin mucin domain (TIM)4 that ligates TIM1 on CD4 T cells to drive them to become Th2 cells, but the pathogenic source of TIM4 is unknown. Here we report that a significant increase in TIM4 expression in human DCs was observed in response to Staphylococcal enterotoxin B (SEB) stimulation via Toll-like receptor (TLR)2 and nucleotide-binding oligomerization domain (NOD)1 pathway. Coculture SEB-conditioned DCs with naïve CD4 T cells induced Th2 responses that could be abolished using TLR2 or NOD1 or TIM4 or TIM1 with counterpart antibodies or RNA interference. The results demonstrate that Staphylococcus aureus derived SEB promotes the TIM4 production in human DCs. The interaction between TIM4 and TIM1 drives naïve CD4 T cells to develop to Th2 cells.
Liu
Tao
T
Allergy Research Unit, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.
He
Shao-Heng
SH
Zheng
Peng-Yuan
PY
Zhang
Tao-Yuan
TY
Wang
Bin-Quan
BQ
Yang
Ping-Chang
PC
D002454:Cell Differentiation / Q000187:drug effects*; D016764:Cell Polarity / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism*; D004768:Enterotoxins / Q000494:pharmacology*; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism
D017077:Culture Media, Conditioned; D004768:Enterotoxins; D008565:Membrane Proteins; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; C512411:TIMD4 protein, human; D051195:Toll-Like Receptor 2; D018664:Interleukin-12; C031818:enterotoxin B, staphylococcal