Lichen planopilaris is characterized by immune privilege collapse of the hair follicle's epithelial stem cell niche
Lichen planopilaris is characterized by immune privilege collapse of the hair follicle's epithelial stem cell niche
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DOI：
10.1002/path.4233
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发表时间：
2013-10-01
影响因子：
7.3
通讯作者：
Paus, Ralf
中科院分区：
文献类型：
--
作者：
Harries, Matthew J.;Meyer, Katja;Paus, Ralf
扁平苔藓（LPP）是一种慢性炎症性疾病，其发病机制尚不清楚，可导致永久性脱发。虽然位于HF上皮免疫保护的生态位中的上皮性毛囊干细胞（eHFSCs）的破坏可能是LPP发病的关键事件，但这仍有待证实。我们验证了膨出免疫特权（IP）崩溃和炎症诱导的eHFSC死亡是LPP发病机制的关键因素的假设。采用定量（免疫）组织形态学、实时定量聚合酶链反应（qRT-PCR）、激光捕获显微解剖和微阵列分析或皮肤器官培养等方法对42例成人LPP患者的病变和非病变头皮进行活检。在蛋白和转录水平上，病变LPP HFs均表现出凸起性IP塌缩（即MHC I类和II类β 2微球蛋白表达增加，TGF β 2和CD200表达减少）。这伴随着th1偏向的细胞毒性T细胞反应(即CD8(+) GranzymeB（+) T细胞和CD123（+）浆细胞样树突状细胞增加，CXCR3表达增加）和干扰素诱导趋化因子表达增加（CXCL9/10/11）。有趣的是，病变LPP eHFSCs的原位增殖和凋亡均增加。微阵列分析显示，活动性LPP中eHFSC特征的缺失和T细胞激活/结合标记的表达增加，而与非病变性LPP hf相比，凸起PPAR转录没有改变。在非病变性LPP皮肤的器官培养中，干扰素γ (IFN γ)诱导凸起性IP塌陷。LPP是研究和预防人上皮干细胞原位免疫破坏的良好模型疾病。这些新发现提出了一种可能性，即LPP代表了一种自身免疫性疾病，在其发病机制中，IFN γ诱导的肿胀性IP塌陷起着重要作用。在治疗上，鼓包IP保护/修复可能有助于更好地管理这种高度难治性瘢痕性脱发。版权所有(c) 2013大不列颠和爱尔兰病理学会。约翰·威利父子有限公司出版。
Lichen planopilaris (LPP) is a chronic inflammatory disease of unknown pathogenesis that leads to permanent hair loss. Whilst destruction of epithelial hair follicle stem cells (eHFSCs) that reside in an immunologically protected niche of the HF epithelium, the bulge, is a likely key event in LPP pathogenesis, this remains to be demonstrated. We have tested the hypotheses that bulge immune privilege (IP) collapse and inflammation-induced eHFSC death are key components in the pathogenesis of LPP. Biopsies of lesional and non-lesional scalp skin from adult LPP patients (n = 42) were analysed by quantitative (immuno)histomorphometry, real-time quantitative polymerase chain reaction (qRT-PCR), laser capture microdissection and microarray analysis, or skin organ culture. At both the protein and transcriptional level, lesional LPP HFs showed evidence for bulge IP collapse (ie increased expression of MHC class I and II, beta 2microglobulin; reduced TGF beta 2 and CD200 expression). This was accompanied by a Th1-biased cytotoxic T cell response (ie increased CD8(+) GranzymeB(+) T cells and CD123(+) plasmacytoid dendritic cells, with increased CXCR3 expression) and increased expression of interferon-inducible chemokines (CXCL9/10/11). Interestingly, lesional LPP eHFSCs showed both increased proliferation and apoptosis in situ. Microarray analysis revealed a loss of eHFSC signatures and increased expression of T cell activation/binding markers in active LPP, while bulge PPAR transcription was unaltered compared to non-lesional LPP HFs. In organ culture of non-lesional LPP skin, interferon-gamma (IFN gamma) induced bulge IP collapse. LPP is an excellent model disease for studying and preventing immune destruction of human epithelial stem cells in situ. These novel findings raise the possibility that LPP represents an autoimmune disease in whose pathogenesis IFN gamma-induced bulge IP collapse plays an important role. Therapeutically, bulge IP protection/restoration may help to better manage this highly treatment-resistant cicatricial alopecia. Copyright (c) 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.