日本慶應(yīng)義塾大學(xué)研究人員最新發(fā)現(xiàn),，如果人為使一種蛋白質(zhì)在未成熟的T細(xì)胞內(nèi)大量表達(dá)，T細(xì)胞就難以分化成輔助性T細(xì)胞17(Th17細(xì)胞),。這項(xiàng)成果有助于治療Th17過(guò)度作用導(dǎo)致的類風(fēng)濕性關(guān)節(jié)炎、多發(fā)性硬化癥等自體免疫疾病,。
根據(jù)慶應(yīng)義塾大學(xué)發(fā)布的新聞公報(bào),，該校醫(yī)學(xué)系教授吉村昭彥領(lǐng)導(dǎo)的小組經(jīng)實(shí)驗(yàn)發(fā)現(xiàn)，未成熟的T細(xì)胞要成熟并分化成Th17細(xì)胞,，蛋白質(zhì)“Eomesodermin”的量必須減少,，如果人為令這種蛋白質(zhì)在未成熟的T細(xì)胞內(nèi)大量表達(dá)，Th17細(xì)胞就會(huì)顯著減少,。
研究人員還發(fā)現(xiàn),，要使“Eomesodermin”的量減少，必須要有一種名為JNK的磷酸化酶,。他們?cè)趯?shí)驗(yàn)中給多發(fā)性硬化癥模型鼠使用JNK阻斷劑,，結(jié)果實(shí)驗(yàn)鼠的癥狀有了明顯改善。
公報(bào)說(shuō),，如果能提高T細(xì)胞中“Eomesodermin”的表達(dá),，或者抑制JNK的活性，就有望研發(fā)出治療自體免疫疾病的新方法。
輔助性T細(xì)胞在免疫系統(tǒng)中承擔(dān)著舉足輕重的作用,，它們會(huì)根據(jù)入侵病原體種類的不同,，分化成Th1、Th2和Th17三種類型中的一種,，進(jìn)而誘導(dǎo)針對(duì)入侵病原體最適合的免疫應(yīng)答,。而另一方面，如果輔助性T細(xì)胞過(guò)度作用就可能引發(fā)自體免疫疾病,。比如,，Th2過(guò)量生成就會(huì)引起花粉或者食物過(guò)敏；而Th17過(guò)度作用會(huì)引發(fā)類風(fēng)濕性關(guān)節(jié)炎,、多發(fā)性硬化癥和牛皮癬等自體免疫疾病,。相關(guān)研究論文發(fā)表在美國(guó)《免疫》雜志網(wǎng)絡(luò)版上。（生物谷Bioon.com）
生物谷推薦原文出處：
Immunity doi:10.1016/j.immuni.2011.02.021
Transcription Factor Smad-Independent T Helper 17 Cell Induction by Transforming-Growth Factor-β Is Mediated by Suppression of Eomesodermin
Kenji Ichiyama, Takashi Sekiya, Naoko Inoue, Taiga Tamiya, Ikko Kashiwagi, Akihiro Kimura, Rimpei Morita, Go Muto, Takashi Shichita, Reiko Takahashi and Akihiko Yoshimura
Summary
Transforming growth factor-β (TGF-β) has been shown to be required for Th17 cell differentiation via Smad-independent mechanisms. The molecular mechanism underlying this pathway remains to be clarified, however. We searched for genes regulated by TGF-β through the Smad-independent pathway by using Smad2 and Smad3 double-deficient T cells and identified the transcription factor Eomesodermin (Eomes), whose expression was suppressed by TGF-β via the c-Jun N-terminal kinase (JNK)-c-Jun signaling pathway. Inhibition of JNK strongly suppressed disease in an in vivo EAE model as well as in vitro Th17 cell induction. Overexpression of Eomes substantially suppressed Th17 cell differentiation, whereas ablation of Eomes expression could substitute for TGF-β in Th17 cell induction in primary T cells. Eomes suppressed Rorc and Il17a promoters by directly binding to the proximal region of these promoters. In conclusion, the suppression of Eomes by TGF-β via the JNK pathway is an important mechanism for Smad-independent Th17 cell differentiation.
Graphical Abstract
Highlights
Suppression of Eomes by TGF-β is an important mechanism for Th17 cell differentiation ? Eomes expression is suppressed by TGF-β via a Smad-independent mechanism ? The JNK-c-Jun pathway suppresses Eomes expression and promotes Th17 cell differentiation ? Eomes directly inhibits RORγt and IL-17A expression through the T-box domain..
