12月29日,，據(jù)《每日科學(xué)》報道,，癢病是一種神經(jīng)退行性疾病,，它可以作為其他由蛋白積累致組織畸形（蛋白質(zhì)?。┘膊〉哪Ｐ?，如阿爾茲海默氏病和帕金森氏病。有關(guān)這些基因的許多問題仍然懸而未決,。在一個新的博士論文研究中,，發(fā)現(xiàn)了數(shù)個與阮蛋白（PrPSc，與疾病的發(fā)展有關(guān)）攝取相關(guān)的因子以及朊蛋白是如何與腸道內(nèi)的免疫細(xì)胞相互作用,。
羊瘙癢病屬于一組被稱為"傳染性海綿狀腦?。═SE）"的疾病，因?yàn)樗鼈兛梢栽趧游飩€體之間傳播,，并導(dǎo)致大腦產(chǎn)生海綿狀,、退行性改變。這些疾病不僅折磨羊,，還折磨牛（牛海綿狀腦病,，又稱瘋牛病，BSE）,、鹿（鹿慢性消耗性疾病,，又稱瘋鹿病，CWD）以及人類（克雅氏病CJD）,。它們在一定程度上也可以在物種見傳播,，在20世紀(jì)90年代，超過200人經(jīng)由食物感染而患上了克雅氏病,。
傳染性海綿狀腦?。═SE），或者稱阮病毒疾病,，被認(rèn)為是感染了一種能致病的蛋白質(zhì)變體--朊蛋白,，它是機(jī)體細(xì)胞的正常組成部分，在腦中含量最為豐富,。一般而言,，阮病毒疾病可能是傳染的、遺傳的或偶發(fā)/自發(fā)的,。當(dāng)正常的朊蛋白突變成致病的變種,，疾病便發(fā)生了，變種朊蛋白在空間結(jié)構(gòu)上與健康的朊蛋白不同,。由于變種的朊蛋白具有不同的空間結(jié)構(gòu),，機(jī)體細(xì)胞很難降解它，因此它就一直在積累,。
因?yàn)殡玫鞍祝≒rPSc）是在疾病早期在腸道系統(tǒng)的淋巴組織中被發(fā)現(xiàn),，推測它是經(jīng)由腸胃道傳染。在獸醫(yī)學(xué)家Caroline Piercey Akesson博士研究期間，研究了朊蛋白在腸道內(nèi)的吸收,，從而對疾病發(fā)展的早期階段所發(fā)生的過程有了新的了解,。與早先的推測相反，她通過免疫電鏡證明阮蛋白不是直接從腸道轉(zhuǎn)運(yùn)到腸道相關(guān)的的淋巴組織,。相反,，她發(fā)現(xiàn)朊蛋白自由地穿過或穿進(jìn)腸道淋巴組織之外的淋巴細(xì)胞。
樹突狀細(xì)胞據(jù)推測發(fā)揮著"看門人"的作用,，它決定機(jī)體能容忍什么以及當(dāng)面對外來物時該策劃哪一種免疫防御反應(yīng),。Akeeson的目標(biāo)之一就是樹突細(xì)胞與朊蛋白攝取之間的相互作用。首先,，需要了解正常的羊腸道內(nèi)樹突狀細(xì)胞的特點(diǎn),；其次,，去調(diào)查哪一類型的細(xì)胞與阮病毒的攝取有關(guān),。
她的研究結(jié)果表明，不是樹突狀細(xì)胞,，而是巨噬細(xì)胞負(fù)責(zé)朊蛋白的攝取,。Akesson的研究揭示，朊蛋白利用了腸道中大分子物質(zhì)攝取的正常生理通道,，這可能對機(jī)體的免疫監(jiān)視系統(tǒng)有顯著影響,。一個可能的后果就是免疫耐受被激活，從而阻礙了腸道對所吸收的朊蛋白的正常免疫反應(yīng),。
今后的研究能夠揭示免疫細(xì)胞是如何運(yùn)輸朊蛋白及機(jī)體是如何處理朊蛋白,，這將具有非常重要的意義，不僅是為了提供更多的關(guān)于癢病的知識,，還為研究人類和其他動物中神經(jīng)退行性蛋白質(zhì)病提供重要見解,。
Caroline Piercey Akesson于12月20日在挪威獸醫(yī)科學(xué)系進(jìn)行了博士論文答辯，論文的題目是：研究阮病毒的攝取及其與羊腸道中免疫細(xì)胞的早期相互作用,。（生物谷bioon.com）
doi:10.1371/journal.pone.0022180
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PMID:
Exosome-producing follicle associated epithelium is not involved in uptake of PrPd from the gut of sheep (Ovis aries): an ultrastructural study.
Akesson CP, McGovern G, Dagleish MP, Espenes A, McL Press C, Landsverk T, Jeffrey M.
Abstract In natural or experimental oral scrapie infection of sheep, disease associated prion protein (PrP(d)) often first accumulates in Peyer's patch (PP) follicles. The route by which infectivity reaches the follicles is unknown, however, intestinal epithelial cells may participate in intestinal antigenic presentation by delivering exosomes as vehicles of luminal antigens. In a previous study using an intestinal loop model, following inoculation of scrapie brain homogenate, inoculum associated PrP(d) was detected by light microscopy shortly (15 minutes to 3.5 hours) after inoculation in the villous lacteals and sub-mucosal lymphatics. No PrP(d) was located within the follicle-associated epithelium (FAE), sub-FAE domes or the PP follicles. To evaluate this gut loop model and the transportation routes in more detail, we used electron microscopy (EM) to study intestinal tissues exposed to scrapie or control homogenates for 15 minutes to 10 days. In addition, immuno-EM was used to investigate whether exosomes produced in the FAE may possess small amounts of PrP(d) that were not detectable by light microscopy. This study showed that the integrity of the intestinal epithelium was sustained in the intestinal loop model. Despite prominent transcytotic activity and exosome release from the FAE of the ileal PP in sheep, these structures were not associated with transportation of PrP(d) across the mucosa. The study did not determine how infectivity reaches the follicles of PPs. The possibility that the infectious agent is transported across the FAE remains a possibility if it occurs in a form that is undetectable by the methods used in this study. Infectivity may also be transported via lymph to the blood and further to all other lymphoid tissues including the PP follicles, but the early presence of PrP(d) in the PP follicles during scrapie infection argues against such a mechanism.
