F1000（Faculty of 1000 Medicine）由美國哈佛大學(xué)和英國劍橋大學(xué)等全世界2500名國際頂級醫(yī)學(xué)教授組成的國際權(quán)威機(jī)構(gòu)。其中近期最受關(guān)注的七篇免疫學(xué)論文如下：
1.解答T細(xì)胞爭論
M.A. Zachariah, J.G. Cyster, "Neural crest-derived pericytes promote egress of mature thymocytes at the corticomedullary junction," Science, 328:1129-35, 2010. Eval by Serge van de Pavert and Reina Mebius, VU Univ Med Center, Netherlands; Ivan Dzhagalov and Ellen Robey, University of California, Berkeley.
這項(xiàng)研究分析了外周細(xì)胞促進(jìn)胸腺T細(xì)胞外出的機(jī)制，文章中使用了Sigma公司的S1P蛋白在transwell遷移試驗(yàn)中來刺激胸腺細(xì)胞。
2.T細(xì)胞活性新機(jī)制
S. Tay et al., "Single-cell NF-kappaB dynamics reveal digital activation and analogue information processing," Nature, 466:267-71, 2010. Eval by Oberdan Leo and Muriel Moser, University of Brussels, Belgium; Yutaka Tagaya, National Cancer Institute.
在信號轉(zhuǎn)導(dǎo)領(lǐng)域里面有那么幾個(gè)挺有名的轉(zhuǎn)錄因子（Transcription factor, TF），比如p53，cMyc，cFos之類的，當(dāng)然NF-kB也是其中一個(gè)，NF-kB最早克隆出來到現(xiàn)在大概二十多年了吧（PS：二十多年了，很多詳細(xì)機(jī)制都還沒搞清楚，怪不得都說生物杯具），早期發(fā)現(xiàn)是這個(gè)TF跟炎癥反應(yīng)很相關(guān)，這個(gè)TF可以轉(zhuǎn)錄出大量的炎癥因子和其他蛋白，具體的list我還沒有查閱文獻(xiàn)，除了炎癥反應(yīng)也會(huì)激活獲得性免疫系統(tǒng)。NF-kB是各個(gè)教材里面說明Nuclear translocation機(jī)制的時(shí)候用得比較多的一個(gè)例子。
NF-kB是靠IkB調(diào)控的，就是IkB被IKK磷酸化激活后會(huì)被泛素化，這個(gè)泛素化是degradative的，然后IkB就被降解掉了，IkB結(jié)合NF-kB的兩個(gè)subunits，一旦降解后，就會(huì)露出兩個(gè)subunits表面的nuclear translocation sequence，會(huì)導(dǎo)致NF-kB轉(zhuǎn)移到細(xì)胞核內(nèi)，然后轉(zhuǎn)錄很多基因，其中比較重要的包括IkB和TNF-alpha，因?yàn)镮kB翻譯后又會(huì)再次結(jié)合NF-kB導(dǎo)致NF-kB轉(zhuǎn)移回細(xì)胞質(zhì)中，所以是個(gè)feedback的過程，這個(gè)過程可以導(dǎo)致NF-kB nuclear translocation oscillation，可以參看第一張圖。
研究人員用不同濃度的TNF-alpha刺激細(xì)胞，然后檢測不同濃度刺激下的NF-kB的dynamics和各種被轉(zhuǎn)錄基因的表達(dá)譜，然后改進(jìn)了原來應(yīng)用于IKK-NF-kB這個(gè)module的數(shù)學(xué)模型。
3.干細(xì)胞與感染
N.N. Belyaev et al., "Induction of an IL7-R(+)c-Kit(hi) myelolymphoid progenitor critically dependent on IFN-gamma signaling during acute malaria," Nat Immunol, 11:477-85, 2010. Eval by Jessy Deshane and David Chaplin, Univ of Alabama at Birmingham; Christian Engwerda Queensland Institute of Medical Research.
4.在遺傳敏感個(gè)體中消化道寄生菌引發(fā)類風(fēng)濕關(guān)節(jié)炎
H.J. Wu et al., "Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells," Immunity, 32:815-27, 2010. Eval by Caio Fagundes and Mauro Teixeira, Universidade Federal De Minas Gerais, Brazil; Allen Ho and Sarah Gaffen, University of Pittsburgh; E Charles Snow, University of Kentucky Medical Center; Rochelle Marie Hinman and John Cambier, National Jewish Medical and Research.
生活在消化道中的一種細(xì)菌能夠引發(fā)免疫級聯(lián)反應(yīng)最終導(dǎo)致關(guān)節(jié)炎的發(fā)生。與大部分哺乳動(dòng)物一樣，人體消化道內(nèi)充滿了數(shù)千種細(xì)菌，大部分是有益菌，幫助形成正常健康的免疫系統(tǒng)。但有時(shí)有些細(xì)菌也會(huì)在導(dǎo)致免疫系統(tǒng)失調(diào)中發(fā)揮作用，特別是攻擊自體細(xì)胞的自身免疫失調(diào)，比如類風(fēng)濕性關(guān)節(jié)炎。哈佛醫(yī)學(xué)院和紐約大學(xué)的研究人員研究發(fā)現(xiàn)在易患關(guān)節(jié)炎的無菌老鼠自體免疫性關(guān)節(jié)炎顯著減弱，而在引入一種細(xì)菌分節(jié)絲狀菌后，就觸發(fā)了導(dǎo)致關(guān)節(jié)炎發(fā)展的自體免疫過程。分節(jié)絲狀菌激活了在無菌時(shí)弱化的Th17細(xì)胞亞群，產(chǎn)生自身抗體，迅速引發(fā)自體免疫性關(guān)節(jié)炎。
5.通過寄生線蟲鼠鞭蟲來探索腸道菌群
K.S. Hayes et al., "Exploitation of the intestinal microflora by the parasitic nematode Trichuris muris," Science, 328:1391-94, 2010. Eval by Paul J Brindley, George Washington University; Adam Savage and Richard Locksley, University of California, San Francisco; Thomas Nutman, National Institutes of Health.
哺乳動(dòng)物腸道棲居生物不僅包括相當(dāng)數(shù)量的共生細(xì)菌，可能還包括體積較大的寄生生物，如蠕蟲和原生動(dòng)物。
某種程度上，所有這些生物會(huì)產(chǎn)生相互作用。我們成功發(fā)現(xiàn)寄生線蟲--鼠鞭蟲在小鼠大腸內(nèi)的慢性感染依賴于微生態(tài)菌群，并與宿主免疫應(yīng)答得調(diào)節(jié)相一致。
通過降低動(dòng)物宿主細(xì)菌的數(shù)量，我們顯著降低了鼠鞭蟲卵的數(shù)量。細(xì)菌（微生態(tài)菌群）和寄生蟲（大型動(dòng)物區(qū)系）的相互作用給腸道生境注入新的動(dòng)力，為我們對腸道內(nèi)穩(wěn)態(tài)和免疫調(diào)節(jié)的概念提供了新的理解。
6.令人驚訝的TB守護(hù)者
S. Shafiani et al., "Pathogen-specific regulatory T cells delay the arrival of effector T cells in the lung during early tuberculosis," J Exp Med, 207:1409-20, 2010. Eval by Stanley Perlman, University of Iowa; Andrea Cooper, Trudeau Institute; Nandini Krishnamoorthy and Anuradha Ray, University of Pittsburgh.
7.Lck酶作用新機(jī)制
K. Nika et al., "Constitutively active Lck kinase in T cells drives antigen receptor signal transduction," Immunity, 32:766-77, 2010. Eval by E Charles Snow, University of Kentucky Medical Center; Larry Kane, University of Pittsburgh
