Klf4 expression in conventional dendritic cells is required for T helper 2 cell responses.

Klf4 expression in conventional dendritic cells is required for T helper 2 cell responses.
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DOI:
10.1016/j.immuni.2015.04.017
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发表时间:
2015-05-19
期刊:
影响因子:
32.4
通讯作者:
Murphy, Kenneth M.
Murphy, Kenneth M.
中科院分区:
医学1区
文献类型:
--
作者:
Tussiwand, Roxane;Everts, Bart;Grajales-Reyes, Gary E.;Kretzer, Nicole M.;Iwata, Arifumi;Bagaitkar, Juhi;Wu, Xiaodi;Wong, Rachel;Anderson, David A.;Murphy, Theresa L.;Pearce, Edward J.;Murphy, Kenneth M.

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经典树突状细胞(cDC)的两个主要谱系表达并需要IRF8或IRF4转录因子用于其发育和功能。IRF8依赖性cDC促进抗病毒和辅助性T细胞1(Th1)应答,而表达IRF4的cDC参与控制Th2和Th17细胞应答。在这里,我们提供了Kruppel样因子4(Klf4)在表达IRF4的cDC中促进体内Th2而不是Th17细胞应答所需的证据。在曼氏血吸虫感染、血吸虫卵抗原(SEA)免疫和屋尘螨攻击(HDM)期间,cDC内的条件性Klf4缺失损害Th2细胞应答,而不影响细胞毒性T淋巴细胞(CTL)、Th1和Th17细胞对单纯疱疹病毒、刚地弓形虫和啮齿类柠檬酸杆菌感染的应答。此外,Klf4缺失降低了前cDC中的IRF4表达,并导致几种组织中表达IRF4的cDC亚群的选择性丧失。这些结果表明Klf4引导促进IRF4表达cDC异质性的转录程序。
The two major lineages of classical dendritic cells (cDCs) express and require either IRF8 or IRF4 transcription factors for their development and function. IRF8-dependent cDCs promote anti-viral and T-helper 1 (Th1) cell responses, whereas IRF4-expressing cDCs have been implicated in controlling both Th2 and Th17 cell responses. Here, we have provided evidence that Kruppel-like factor 4 (Klf4) is required in IRF4-expressing cDCs to promote Th2 but not Th17 cell responses in vivo. Conditional Klf4 deletion within cDCs impaired Th2 cell responses during Schistosoma mansoni infection, Schistosoma egg antigen (SEA) immunization, and house dust mite challenge (HDM), without affecting cytotoxic T lymphocyte (CTL), Th1 and Th17 cell responses to herpes simplex virus, Toxoplasma gondii and Citrobacter rodentium infections. Further, Klf4 deletion reduced IRF4 expression in pre-cDCs and resulted in selective loss of IRF4-expressing cDCs subsets in several tissues. These results indicate that Klf4 guides a transcriptional program promoting IRF4-expressing cDCs heterogeneity.
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