IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells.
IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells.
复制标题
DOI：
10.1038/ni.1677
复制
发表时间：
2008-12
影响因子：
30.5
通讯作者：
Kuchroo, Vijay K.
中科院分区：
文献类型：
--
作者：
Dardalhon, Valerie;Awasthi, Amit;Kwon, Hyoung;Galileos, George;Gao, Wenda;Sobel, Raymond A.;Mitsdoerffer, Meike;Strom, Terry B.;Elyaman, Wassim;Ho, I-Cheng;Khoury, Samia;Oukka, Mohamed;Kuchroo, Vijay K.
Foxp3是一种关键的转录因子，参与调节性T细胞（Treg）的产生和功能。转化生长因子β（TGF - β）诱导Foxp3，从而使初始T细胞产生诱导性Foxp3⁺ Treg细胞，而白细胞介素6（IL - 6）抑制诱导性Treg细胞的产生，并诱导产生白细胞介素17（IL - 17）的辅助性T细胞（TH - 17细胞）。然而，白细胞介素4（IL - 4）在TGF - β诱导的Treg细胞产生和/或效应CD4⁺辅助性T细胞产生中的作用尚未得到研究。在此，我们发现IL - 4阻断了TGF - β诱导的Foxp3⁺ Treg细胞的产生。相反，IL - 4诱导了一群主要产生IL - 9和IL - 10的辅助性T细胞。尽管产生大量IL - 10，但IL - 9⁺IL - 10⁺ T细胞未表现出任何调节特性。将产生IL - 9⁺IL - 10⁺的T细胞过继转移到RAG - 1缺陷小鼠体内会诱发结肠炎和周围神经炎。有趣的是，当将IL - 9⁺IL - 10⁺ T细胞与CD45RBhi CD4⁺效应T细胞共同转移到RAG - 1缺陷小鼠体内时，组织炎症的严重程度会加重，这表明IL - 9⁺IL - 10⁺ T细胞不具有任何抑制功能，因此构成了一种独特的产生IL - 10的辅助性效应T细胞群，会促进组织炎症。
Foxp3 is a key transcription factor involved in the generation and function of regulatory T (Treg) cells. Transforming growth factor β (TGF-β) induces Foxp3, which generates inducible Foxp3+ Treg cells from naïve T cells, and interleukin 6 (IL-6) inhibits the generation of inducible Treg cells and induces T helper cells that produce IL-17 (TH-17 cells). However, a role for IL-4 in the generation of TGF-β-induced Treg cells and/or the generation of effector CD4+ T helper cells has not been studied. Here, we show that IL-4 blocked the generation of TGF-β-induced Foxp3+ Treg cells. Instead, IL-4 induced a population of T helper cells that predominantly produce IL-9 and IL-10. The IL-9+IL-10+ T cells did not exhibit any regulatory properties in spite of producing large quantities of IL-10. Adoptive transfer of IL-9+IL-10+producing T cells into RAG-1-deficient mice induced colitis and peripheral neuritis. Interestingly, the severity of tissue inflammation was aggravated when IL-9+IL-10+ T cells were co-transferred with CD45RBhi CD4+ effector T cells into RAG-1-deficient mice, which indicated that IL-9+IL-10+ T cells do not display any suppressive function and therefore constitute a unique population of IL-10-producing helper-effector T cells that promote tissue inflammation.
登录
查看更多内容
影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
DOI：
10.1084/jem.179.1.305
发表时间：
1994-01-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ishida H;Muchamuel T;Sakaguchi S;Andrade S;Menon S;Howard M
通讯作者：
Howard M
影响因子：
15.3
作者：
Apostolou, I;von Boehmer, H
通讯作者：
von Boehmer, H
影响因子：
15.3
作者：
Fahlén, L;Read, S;Gorelik, L;Hurst, SD;Coffman, RL;Flavell, RA;Powrie, F
通讯作者：
Powrie, F
影响因子：
32.4
作者：
Kamanaka, Masahito;Kim, Sean T.;Flavell, Richard A.
通讯作者：
Flavell, Richard A.