來(lái)自德國(guó)慕尼黑大學(xué),、德國(guó)Campus Kiel Schleswig-Holstein大學(xué)醫(yī)學(xué)中心,、伯恩大學(xué)及美國(guó)加州大學(xué)的研究人員組成的一個(gè)研究小組在新研究中揭示了牛皮癬的炎癥機(jī)理，并詳細(xì)地解析了維生素D對(duì)抗這種炎癥反應(yīng)的機(jī)制。相關(guān)研究論文在線發(fā)布在5月11日《科學(xué)》雜志旗下的子刊《科學(xué)—轉(zhuǎn)化醫(yī)學(xué)》（Science translational medicine）雜志上,。
牛皮癬,，又名銀屑病，是一種常見(jiàn)的慢性皮膚病,，其特征是出現(xiàn)大小不等的丘疹,，紅斑，表面覆蓋著銀白色鱗屑,，邊界清楚,。據(jù)調(diào)查，銀屑病的發(fā)病率占據(jù)全世界人口的0.1%-3%,。由于該病頑固難治,，被列為當(dāng)今世界皮膚科領(lǐng)域的重要研究課題，是全世界皮膚科重點(diǎn)防治疾病之一,。過(guò)去的研究表明,，牛皮癬的發(fā)生是因?yàn)闄C(jī)體的免疫系統(tǒng)發(fā)出了虛假的危險(xiǎn)信號(hào)，這些信號(hào)可激活被稱作炎性體的蛋白復(fù)合體并提高機(jī)體對(duì)損傷的炎癥反應(yīng),，導(dǎo)致皮膚上的牛皮癬塊的爆發(fā),。近期亦有研究證實(shí)自由流動(dòng)的或細(xì)胞質(zhì)中的DNA與牛皮癬的炎癥有關(guān)。
在這篇文章中,，Jürgen Schauber及其同事從牛皮癬患者身上進(jìn)行皮膚活檢,，并將有病的皮膚細(xì)胞與健康志愿者者的皮膚細(xì)胞進(jìn)行比較，證實(shí)在牛皮癬患者的角質(zhì)化細(xì)胞中具有大量的細(xì)胞溶質(zhì)DNA,。通過(guò)從皮膚樣本中萃取RNA并對(duì)其基因表達(dá)的水平進(jìn)行檢查后,，研究人員發(fā)現(xiàn)一種編碼某個(gè)被稱作AIM2受體的基因在罹患牛皮癬病人的皮膚中被高度激活。 AIM2 與其它蛋白合作而組裝成為炎性體,。 該炎性體接著會(huì)激活白細(xì)胞介素1β，這是驅(qū)動(dòng)炎癥的主要物質(zhì)之一,。
在進(jìn)一步的研究中,，Jürgen Schauber等證實(shí)一種稱之為cathelicidin LL-37的抗菌肽能夠與DNA結(jié)合，中和角質(zhì)化細(xì)胞中的細(xì)胞溶質(zhì)DNA,，阻斷AIM2炎性體激活,。進(jìn)而研究人員發(fā)現(xiàn)維生素D控制著皮膚中cathelicidin的產(chǎn)生，并能增加cathelicidin與DNA的結(jié)合,。 維生素D通過(guò)增進(jìn)cathelicidin與DNA的結(jié)合而幫助防止了DNA對(duì)AIM2 受體和觸發(fā)炎癥反應(yīng)的炎性體的激活,。
目前人們常采用外用性維生素D及UVB射線（它可激活維生素D）來(lái)治療牛皮癬這一慢性、自身免疫性皮膚病,。新研究發(fā)現(xiàn)幫助解釋了維生素D療法為何能夠成功地治療牛皮癬及注入皮膚干燥或濕疹等相關(guān)性皮膚病,，即維生素D對(duì)抗牛皮癬炎癥反應(yīng)的機(jī)制，并為這一慢性皮膚疾病提供了新的有潛力的治療靶點(diǎn)。（生物谷Bioon.com）
生物谷推薦原文：
Science Translational Medicine DOI： 10.1126/scitranslmed.3002001
Cytosolic DNA Triggers Inflammasome Activation in Keratinocytes in Psoriatic Lesions
Dombrowski, Yvonne; Peric, Mark; Koglin, Sarah; Kammerbauer, Claudia; G??, Christine; Anz, David; Simanski, Maren; Gl?ser, Regine; Harder, Jürgen; Hornung, Veit; Gallo, Richard L.; Ruzicka, Thomas; Besch, Robert; Schauber, Jürgen
The proinflammatory cytokine interleukin-1β (IL-1β) plays a central role in the pathogenesis and the course of inflammatoryskin diseases, including psoriasis. Posttranscriptional activation of IL-1β is mediated by inflammasomes; however, the mechanismstriggering IL-1β processing remain unknown. Recently, cytosolic DNA has been identified as a danger signal that activatesinflammasomes containing the DNA sensor AIM2. In this study, we detected abundant cytosolic DNA and increased AIM2 expression in keratinocytes in psoriatic lesions but not in healthy skin. In cultured keratinocytes, interferon-γ inducedAIM2, and cytosolic DNA triggered the release of IL-1β via the AIM2 inflammasome. Moreover, the antimicrobial cathelicidin peptideLL-37, which can interact with DNA in psoriatic skin, neutralized cytosolic DNA in keratinocytes and blocked AIM2 inflammasomeactivation. Together, these data suggest that cytosolic DNA is an important disease-associated molecular pattern that cantrigger AIM2 inflammasome and IL-1β activation in psoriasis. Furthermore, cathelicidin LL-37 interfered with DNA-sensing inflammasomes,which thereby suggests an anti-inflammatory function for this peptide. Thus, our data reveal a link between the AIM2 inflammasome,cathelicidin LL-37, and autoinflammation in psoriasis, providing new potential targets for the treatment of this chronic skindisease.
