Krüppel-like factor 2 regulates trafficking and homeostasis of gammadelta T cells.

Krüppel-like factor 2 regulates trafficking and homeostasis of gammadelta T cells.
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DOI:
10.4049/jimmunol.1000511
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发表时间:
2010-06-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Hogquist KA
Hogquist KA
中科院分区:
其他
文献类型:
--
作者:
Odumade OA;Weinreich MA;Jameson SC;Hogquist KA

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γδ T细胞在胸腺中产生,并运输至次级淋巴器官和上皮表面,在那里它们调节免疫应答。αβ T细胞需要脂质受体S1P1和CD62L,用于胸腺迁移和通过次级淋巴器官的循环。这两个基因在常规αβ T细胞中都受到转录因子KLF2的调控。目前尚不清楚γδ T细胞是否使用类似的机制。在这项研究中,我们发现胸腺γδ T细胞表达S1P1,并且它受KLF2的调节。此外,KLF2和S1P1缺陷的γδ T细胞在胸腺中积累,并且不能在次级淋巴器官或肠道中聚集,这与已发表的工作的预期相反。有趣的是,KLF2而不是S1P1缺陷导致通常罕见的CD4+ PLZF+“γδ NKT细胞”群体的扩增。因此,KLF2对于γδ T细胞的稳态和运输至关重要。
γδ T cells are generated in the thymus and traffic to secondary lymphoid organs and epithelial surfaces where they regulate immune responses. αβ T cells require the lipid receptor, S1P1 and CD62L, for thymic emigration and circulation through secondary lymphoid organs. Both of these genes are regulated by the transcription factor KLF2 in conventional αβ T cells. It is unclear if γδ T cells use similar mechanisms. In this study, we show that thymic γδ T cells express S1P1, and that it is regulated by KLF2. Furthermore, KLF2 and S1P1-deficient γδ T cells accumulate in the thymus and fail to populate the secondary lymphoid organs or gut, in contrast to the expectation from published work. Interestingly, KLF2 but not S1P1 deficiency led to the expansion of a usually rare population of CD4+ PLZF+ “γδ NKT cells”. Thus KLF2 is critically important for the homeostasis and trafficking of γδ T cells.
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