T淋巴細(xì)胞在免疫系統(tǒng)中發(fā)揮著重要功能,。浙江大學(xué)醫(yī)學(xué)院免疫學(xué)研究所魯林榮教授帶領(lǐng)的研究團(tuán)隊(duì)近日在T淋巴細(xì)胞中發(fā)現(xiàn)并命名一個(gè)名叫Tespa1的新基因,，并闡釋了其作用機(jī)制。
相關(guān)論文“Tespa1 is involved in late thymocyte development through regulation of the TCR-mediated signaling”5月6日在線發(fā)表在《自然-免疫學(xué)》(Nature Immunology)上,，第一作者為浙大醫(yī)學(xué)院副教授王迪和博士生鄭明珠，浙大醫(yī)學(xué)院免疫學(xué)研究所和基礎(chǔ)系PMCB團(tuán)隊(duì)PI魯林榮為通訊作者,。
人體免疫系統(tǒng)依賴(lài)各種高度分化的免疫細(xì)胞來(lái)抵御外界微生物的感染,。其中，T淋巴細(xì)胞在免疫反應(yīng)中擔(dān)當(dāng)重要的角色,，它們能直接殺傷病毒感染細(xì)胞或腫瘤細(xì)胞,，或輔助B細(xì)胞產(chǎn)生抗體,，對(duì)特異性抗原產(chǎn)生應(yīng)答并分泌效應(yīng)因子等，是機(jī)體抵御感染和腫瘤形成的重要細(xì)胞亞群,。T細(xì)胞的功能異常會(huì)導(dǎo)致機(jī)體免疫功能的紊亂并誘發(fā)多種疾?。喝缦忍煨訲細(xì)胞缺陷會(huì)導(dǎo)致嬰兒細(xì)胞免疫功能缺失，易患真菌,、病毒,、原蟲(chóng)等感染，嚴(yán)重的在3-4個(gè)月就會(huì)因感染而死亡,；同時(shí)T細(xì)胞免疫缺陷者的腫瘤發(fā)病率是正常人100-300倍,；而大家熟知的艾滋病就是因?yàn)镠IV病毒就是通過(guò)攻擊人體的CD4 T細(xì)胞使其喪失功能，進(jìn)而導(dǎo)致獲得性免疫缺陷,。
T淋巴細(xì)胞在胸腺中發(fā)育,，該過(guò)程受到精細(xì)的細(xì)胞和分子水平調(diào)控。魯林榮課題組通過(guò)生物信息學(xué)篩選,，發(fā)現(xiàn)Tespa1基因在胸腺中有特異性表達(dá),。隨后，研究人員通過(guò)構(gòu)建Tespa1基因敲除小鼠,，發(fā)現(xiàn)小鼠中Tespa1基因的缺失會(huì)導(dǎo)致T細(xì)胞發(fā)育受阻,。進(jìn)一步的顯示，Tespa1對(duì)于指導(dǎo)T細(xì)胞發(fā)育的T細(xì)胞受體（TCR）信號(hào)傳導(dǎo)起著精細(xì)的調(diào)控作用,。
“這項(xiàng)研究擴(kuò)充了我們目前對(duì)T細(xì)胞發(fā)育和T細(xì)胞信號(hào)傳導(dǎo)的認(rèn)識(shí),，同時(shí)也為T(mén)淋巴細(xì)胞相關(guān)疾病的臨床診斷和治療提供了新的研究靶點(diǎn)和思路。”魯林榮教授介紹,，接下來(lái),，研究團(tuán)隊(duì)將在患有免疫缺陷或免疫功能紊亂的病人中調(diào)查有無(wú)Tespa1基因的突變，探究這種基因與人體疾病的相互關(guān)聯(lián),。“如果存在關(guān)聯(lián),，那么Tespa1基因可以作為今后這類(lèi)疾病基因診斷和靶向治療的重要指標(biāo)。”(生物谷：Bioon.com)
doi:10.1038/ni.2301
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Tespa1 is involved in late thymocyte development through the regulation of TCR-mediated signaling
Di Wang, Mingzhu Zheng, Lei Lei, Jian Ji, Yunliang Yao, Yuanjun Qiu, Lie Ma, Jun Lou, Chuan Ouyang, Xue Zhang, Yuewei He, Jun Chi, Lie Wang, Ying Kuang, Jianli Wang, Xuetao Cao & Linrong Lu
Signaling via the T cell antigen receptor (TCR) during the CD4+CD8+ double-positive developmental stage determines thymocyte selection and lineage commitment. Here we describe a previously uncharacterized T cell–expressed protein, Tespa1, with critical functions during the positive selection of thymocytes. Tespa1−/− mice had fewer mature thymic CD4+ and CD8+ T cells, which reflected impaired thymocyte development. Tespa1 associated with the TCR signaling components PLC-γ1 and Grb2, and Tespa1 deficiency resulted in attenuated TCR signaling, as reflected by defective activation of the Erk–AP-1 and Ca2+-NFAT pathways. Our findings demonstrate that Tespa1 is a component of the TCR signalosome and is essential for T cell selection and maturation through the regulation of TCR signaling during T cell development.
