Induction of hyper Th1 cell-type immune responses by dendritic cells lacking the suppressor of cytokine signaling-1 gene
Induction of hyper Th1 cell-type immune responses by dendritic cells lacking the suppressor of cytokine signaling-1 gene
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DOI：
10.4049/jimmunol.174.7.4325
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发表时间：
2005-04-01
影响因子：
4.4
通讯作者：
Yoshimura, A
中科院分区：
文献类型：
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作者：
Hanada, T;Tanaka, K;Yoshimura, A
细胞因子信号转导抑制因子（SOCS 1/JAB）在调节树突状细胞（DC）功能、抑制炎症性疾病和系统性自身免疫中发挥重要作用。然而，SOCS 1在DC中启动Th细胞应答的作用尚未阐明。在这里，我们证明，SOCSI缺陷的DC诱导更强的Th 1型反应在体外和体内。在体外，SOCSI缺陷型DC比野生型（WT）DC诱导更高的来自初始T细胞的IFN-γ产生。当体内转移SOCS 1缺陷型骨髓来源的DC（BMDC）时，淋巴结T细胞也产生更大量的IFN-γ。此外，SOCS 1（-/-）BMDCs比WT BMDCs提高了更有效的抗肿瘤免疫。微阵列分析显示，WN诱导的基因在SOCS 1缺陷的DC中高度表达，而没有IFN刺激，这表明在SOCS 1（-/-）DC中的超STAT 1激活。这些SOCS 1缺陷型DC的表型与CD 8 α（+）DC的表型相似，并且在WT脾中，SOCS 1在Th 2诱导的CD 4（+）DC亚群中的表达水平高于Th 1诱导的CD 8 α（+）DC亚群。我们认为SOCS 1基因在DC中表达的减少导致CD 8 α（+）DC样表型，其促进Th 1型超应答。
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 autoimmunitv. However, role of SOCS1 in DCs for the initiation of Th cell response has not been clarified. Here we demonstrate that SOCSI-deficient DCs induce stronger Th1-type responses both in vitro and in vivo. SOCSI-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 WN-inducible genes were highly expressed in SOCSI-deficient DCs without IFN stimulation, suggesting hyper STAT1 activation in SOCS1(-/-) DCs. These phenotypes of SOCS1-deficient DCs were similar to those of CD8 alpha(+) DCs, and in the WT spleen, SOCS1 is expressed at higher levels in the Th2-inducing CD4(+) DC subset, relative to the Th1-inducing CD8 alpha(+) DC subset. We propose that reduction of the SOCS1 gene expression in DCs leads to CD8 alpha(+) DC-like phenotype which promotes Th1-type hyperresponses.