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白细胞介素-4抑制转化生长因子-β诱导的叉头框蛋白3阳性T细胞，并与转化生长因子-β共同产生白细胞介素-9阳性、白细胞介素-10阳性、叉头框蛋白3阴性效应T细胞。

IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells.

作者信息

Dardalhon Valérie, 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

机构信息

Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA.

出版信息

Nat Immunol. 2008 Dec;9(12):1347-55. doi: 10.1038/ni.1677. Epub 2008 Nov 9.

DOI:10.1038/ni.1677
PMID:18997793
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2999006/
Abstract

Transcription factor Foxp3 is critical for generating regulatory T cells (T(reg) cells). Transforming growth factor-beta (TGF-beta) induces Foxp3 and suppressive T(reg) cells from naive T cells, whereas interleukin 6 (IL-6) inhibits the generation of inducible T(reg) cells. Here we show that IL-4 blocked the generation of TGF-beta-induced Foxp3(+) T(reg) cells and instead induced a population of T helper cells that produced IL-9 and IL-10. The IL-9(+)IL-10(+) T cells demonstrated no regulatory properties despite producing abundant IL-10. Adoptive transfer of IL-9(+)IL-10(+) T cells into recombination-activating gene 1-deficient mice induced colitis and peripheral neuritis, the severity of which was aggravated if the IL-9(+)IL-10(+) T cells were transferred with CD45RB(hi) CD4(+) effector T cells. Thus IL-9(+)IL-10(+) T cells lack suppressive function and constitute a distinct population of helper-effector T cells that promote tissue inflammation.

摘要

转录因子Foxp3对于调节性T细胞（Treg细胞）的产生至关重要。转化生长因子-β（TGF-β）可诱导初始T细胞产生Foxp3和抑制性Treg细胞，而白细胞介素6（IL-6）则抑制诱导性Treg细胞的产生。在此，我们发现IL-4可阻断TGF-β诱导的Foxp3+ Treg细胞的产生，转而诱导一群产生IL-9和IL-10的辅助性T细胞。尽管IL-9+IL-10+ T细胞产生大量IL-10，但并未表现出调节特性。将IL-9+IL-10+ T细胞过继转移至重组激活基因1缺陷小鼠可诱发结肠炎和周围神经炎，若将IL-9+IL-10+ T细胞与CD45RBhi CD4+效应性T细胞一同转移，则病情会加重。因此，IL-9+IL-10+ T细胞缺乏抑制功能，构成了促进组织炎症的独特辅助效应性T细胞群体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f37/2999006/a05b237a061b/nihms184364f4a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f37/2999006/437f7df3fd4e/nihms184364f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f37/2999006/c2b94cd17340/nihms184364f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f37/2999006/78e1693b1177/nihms184364f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f37/2999006/a05b237a061b/nihms184364f4a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f37/2999006/437f7df3fd4e/nihms184364f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f37/2999006/c2b94cd17340/nihms184364f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f37/2999006/78e1693b1177/nihms184364f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f37/2999006/a05b237a061b/nihms184364f4a.jpg

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