Induction of regulatory properties in dendritic cells by Valpha14 NKT cells.
Valpha14 NKT cells exhibit various immune regulatory properties in vivo, but their precise mechanisms remain to be solved. In this study, we demonstrate the mechanisms of generation of regulatory dendritic cells (DCs) by stimulation of Valpha14 NKT cells in vivo. After repeated injection of alpha-galactosylceramide (alpha-GalCer) into mice, splenic DCs acquired properties of regulatory DCs in IL-10-dependent fashion, such as nonmatured phenotypes and increased IL-10 but reduced IL-12 production. The unique cytokine profile in these DCs appears to be regulated by ERK1/2 and IkappaB(NS). These DCs also showed an ability to suppress the development of experimental allergic encephalomyelitis by generating IL-10-producing regulatory CD4 T cells in vivo. These findings contribute to explaining how Valpha14 NKT cells regulate the immune responses in vivo.
Kojo
Satoshi
S
Laboratory for Immune Regulation, Research Center for Allergy and Immunology (RCAI), Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
Seino
Ken-Ichiro
K
Harada
Michishige
M
Watarai
Hiroshi
H
Wakao
Hiroshi
H
Uchida
Tetsuro
T
Nakayama
Toshinori
T
Taniguchi
Masaru
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage / Q000494:pharmacology; D020672:I-kappa B Proteins / Q000502:physiology; D007111:Immunity, Cellular; D016753:Interleukin-10 / Q000096:biosynthesis / Q000494:pharmacology; D018664:Interleukin-12 / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology
D005699:Galactosylceramides; D020672:I-kappa B Proteins; C493154:alpha-galactosylceramide; D016753:Interleukin-10; D018664:Interleukin-12; D048052:Mitogen-Activated Protein Kinase 3