10月27日,，歐洲免疫學(xué)雜志(European Journal of Immunology)在線發(fā)表了中科院上海生科院生化與細(xì)胞所劉小龍研究組的研究論文“Interferon regulatory factor 4 regulates thymocyte differentiation by repressing Runx3 expression”。
胸腺細(xì)胞在胸腺中定向分化為CD4 和CD8 兩個T細(xì)胞類群,，在建立免疫功能的同時,，獲得自身免疫耐受性,。然而，調(diào)控CD4/CD8細(xì)胞分化定向的分子機(jī)制仍然知之甚少,。干擾素調(diào)節(jié)因子4（IRF4）一直被認(rèn)為只在成熟的淋巴細(xì)胞中表達(dá),，維持著CD4 T細(xì)胞的功能、分化及自穩(wěn)平衡,；而其在胸腺細(xì)胞分化成熟過程中的作用尚未涉及,。
劉小龍研究組研究發(fā)現(xiàn)，在胸腺細(xì)胞分化成熟過程中,，IRF4的表達(dá)受TCR信號調(diào)控,；并且在CD4 SP 和CD8 SP細(xì)胞中差異表達(dá)。轉(zhuǎn)基因小鼠模型實(shí)驗(yàn)表明,，T細(xì)胞特異性過表達(dá)IRF4促進(jìn)CD4定向并抑制CD8定向,；他們的研究還表明，IRF4招募組蛋白去乙?；窰DAC1,，通過直接結(jié)合到CD8細(xì)胞分化決定因子Runx3的基因的遠(yuǎn)端啟動子上，使其組蛋白去乙?；?，從而抑制Runx3的表達(dá)。他們的研究結(jié)果揭示了IRF4調(diào)控胸腺細(xì)胞分化成熟的機(jī)制：持續(xù)的TCR信號促進(jìn)IRF4的表達(dá),，IRF4通過抑制Runx3的轉(zhuǎn)錄,，抑制CD8定向相關(guān)分子的表達(dá)，促進(jìn)胸腺細(xì)胞定向分化為CD4 T細(xì)胞,。該研究還將胸腺細(xì)胞的定向分化與免疫功能關(guān)聯(lián)起來,。
該研究工作得到國家自然科學(xué)基金委，中國科學(xué)院和科技部重大科學(xué)研究計(jì)劃的經(jīng)費(fèi)資助,。（生物谷Bioon.com）
生物谷推薦英文摘要：
European Journal of Immunology DOI: 10.1002/eji.201040570
Interferon regulatory factor 4 regulates thymocyte differentiation by repressing Runx3 expression
Yonghao Cao1,?, Hai Li1,?, Yang Sun1, Xufeng Chen1, Haifeng Liu1, Xiang Gao2, Xiaolong Liu1,*
The transcription factor interferon regulatory factor 4 (IRF4) was originally found to be preferentially expressed in lymphoid cells and to be required for the function, differentiation, and homeostasis of both mature T and B lymphocytes. Recent studies have indicated that IRF4 is also involved in early B-cell development. However, the role of IRF4 in intrathymic T-cell development remains unknown. In this study, we show that IRF4 is upregulated in TCR-signaled thymocytes and is predominantly expressed in CD4 single-positive (SP), but not in CD8 SP, cells. T-cell-specific overexpression of IRF4 impaired the generation and maturation of CD8 SP thymocytes. Further analysis revealed that IRF4 selectively bound to the distal promoter region of Runx3 and repressed its transcription, probably through the deacetylation of histones H3 and H4 in intermediate CD4+CD8low cells and CD4 SP thymocytes. Similar to the effect of Runx3 deficiency, transgenic expression of IRF4 led not only to an aberrantly high expression of CD4 surface molecules on intermediate CD4+CD8low cells and CD8 SP thymocytes, but also impaired CD8+ T-cell function. Taken together, our data suggest that IRF4 plays an important role in the regulation of Runx3 expression and CD4+/CD8+ thymocyte differentiation.
