Targeted NF-kappaB inhibition of asthmatic serum-mediated human monocyte-derived dendritic cell differentiation in a transendothelial trafficking model.
Transendothelial trafficking model mimics in vivo differentiation of monocytes into dendritic cells (DC). The serum from patients with systemic lupus erythematosus promotes the differentiation of monocytes into mature DC. We have shown that selective inhibition of NF-kappaB by adenoviral gene transfer of a novel mutated IkappaBalpha (AdIkappaBalphaM) in DC contributes to T cell tolerance. Here we demonstrated for the first time that asthmatic serum facilitated human monocyte-derived DC (MDDC) maturation associated with increased NF-kappaB activation in this model. Furthermore, selective blockade of NF-kappaB by AdIkappaBalphaM in MDDC led to increased apoptosis, and decreased levels of CD80, CD83, CD86, and IL-12 p70 but not IL-10 in asthmatic serum-stimulated MDDC, accompanied by reduced proliferation of T cells. These results suggest that AdIkappaBalphaM-transferred MDDC are at a more immature stage which is beneficial to augment the immune tolerance in asthma.
Gu
Xiao-Yan
XY
Department of Respiratory Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
Zhou
Lin-Fu
LF
Zhang
Ming-Shun
MS
Dai
Wen-Jing
WJ
Chen
Sai-Ying
SY
He
Shao-Heng
SH
Ji
Xiao-Hui
XH
Yin
Kai-Sheng
KS
D000328:Adult; D001249:Asthma / Q000097:blood / Q000276:immunology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007108:Immune Tolerance; D015847:Interleukin-4 / Q000276:immunology; D008297:Male; D018613:Microscopy, Confocal; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism*
D016328:NF-kappa B; D015847:Interleukin-4; D051550:I-kappa B Kinase