Induction of hyper Th1 cell-type immune responses by dendritic cells lacking the suppressor of cytokine signaling-1 gene.
Suppressor of cytokine signaling (SOCS1/JAB) has been shown to play an important role in regulating dendritic cell (DC) function and suppressing inflammatory diseases and systemic autoimmunity. However, role of SOCS1 in DCs for the initiation of Th cell response has not been clarified. Here we demonstrate that SOCS1-deficient DCs induce stronger Th1-type responses both in vitro and in vivo. SOCS1-deficient DCs induced higher IFN-gamma production from naive T cells than wild-type (WT) DCs in vitro. Lymph node T cells also produced a higher amount of IFN-gamma when SOCS1-deficient bone marrow-derived DCs (BMDCs) were transferred in vivo. Moreover, SOCS1(-/-) BMDCs raised more effective anti-tumor immunity than WT BMDCs. Microarray analysis revealed that IFN-inducible genes were highly expressed in SOCS1-deficient DCs without IFN stimulation, suggesting hyper STAT1 activation in SOCS1(-/-) DCs. These phenotypes of SOCS1-deficient DCs were similar to those of CD8alpha(+) DCs, and in the WT spleen, SOCS1 is expressed at higher levels in the Th2-inducing CD4(+) DC subset, relative to the Th1-inducing CD8alpha(+) DC subset. We propose that reduction of the SOCS1 gene expression in DCs leads to CD8alpha(+) DC-like phenotype which promotes Th1-type hyperresponses.
Hanada
Toshikatsu
T
Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Tanaka
Kentaro
K
Matsumura
Yumiko
Y
Yamauchi
Moriyasu
M
Nishinakamura
Hitomi
H
Aburatani
Hiroyuki
H
Mashima
Ryuichi
R
Kubo
Masato
M
Kobayashi
Takashi
T
Yoshimura
Akihiko
A
D000818:Animals; D016827:CD8 Antigens / Q000032:analysis; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology* / Q000637:transplantation; D007109:Immunity; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D051379:Mice; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D050794:STAT1 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D018417:Th1 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000378:metabolism
D016827:CD8 Antigens; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; C491590:Socs1 protein, mouse; C494080:Stat1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D007371:Interferon-gamma