Critical roles of interferon regulatory factor 4 in CD11bhighCD8α- dendritic cell development

Critical roles of interferon regulatory factor 4 in CD11bhighCD8α- dendritic cell development
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DOI:
10.1073/pnas.0402139101
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发表时间:
2004-06-15
影响因子:
11.1
通讯作者:
Kumatori, A
Kumatori, A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Suzuki, S;Honma, K;Kumatori, A

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干扰素调节因子(IRFs)是一个转录因子家族,在免疫系统的稳态和功能中发挥重要作用。最近的研究表明,IRF-8对于CD 11b(低)CD 8 alpha(+)常规树突状细胞(DC)和浆细胞样DC的发育至关重要。在这里,我们表明IRF-4是重要的CD 11b(高)CD 8 α(-)的传统的DC。在添加GM-CSF或Flt 3配体的两种培养体系中,IRF-4(-/-)小鼠骨髓中CD 11b(高)DC的发育严重受损。在IRF-4(-/-)脾脏中,CD 4(+)CD 8 α(-)DC(CD 11b(高)DC的主要亚群)数量严重减少。IRF-4和IRF-8分别在大多数CD 11b(高)CD 4(+)CD 8 α(-)DC和CD 11b(低)CD 8 α(+)DC中以相互排斥的方式表达。这些结果意味着IRF-4和IRF-8选择性地在表达它们的DC亚群的发育中发挥关键作用。
IFN regulatory factors (IRFs) are a family of transcription factors that play an essential role in the homeostasis and function of immune systems. Recent studies indicated that IRF-8 is critical for the development of CD11b(low)CD8alpha(+) conventional dendritic cells (DCs) and plasmacytoid DCs. Here we show that IRF-4 is important for CD11b(high)CD8alpha(-) conventional DCs. The development of CD11b(high) DCs from bone marrow of IRF-4(-/-) mice was severely impaired in two culture systems supplemented with either GM-CSF or Flt3-ligand. In the IRF-4(-/-) spleen, the number of CD4(+)CD8alpha(-) DCs, a major subset of CD11b(high) DCs, was severely reduced. IRF-4 and IRF-8 were expressed in the majority of CD11b(high) CD4(+)CD8alpha(-) DCs and CD11b(low)CD8alpha(+) DCs, respectively, in a mutually exclusive manner. These results imply that IRF-4 and IRF-8 selectively play critical roles in the development of the DC subsets that express them.