Associations between mast cells and laminin in oral lichen planus

Mast cell numbers are increased significantly in oral lichen planus (OLP). In other inflammatory conditions, mast cells frequently adhere to extracellular matrix proteins such as laminin. The aim of this study, therefore, was to determine whether the distribution of mast cells in OLP is related topographically to laminin in vascular and epithelial basement membranes. Monoclonal antibodies for tryptase, laminin and the α6β1 CD49f laminin-binding integrin were used to identify mast cells, basement membranes (blood vessels and basal epithelium) and the "classical" laminin adhesion receptor, respectively. A double-labelling immunoperoxidase technique was employed to examine and compare mast cell-laminin relationships in OLP (n=19) and normal buccal mucosa (NBM, n=13). In both OLP and NBM, the majority of mast cells were located close to vascular basement membranes. Quantitative studies revealed that the number of mast cells associated with the laminin of vascular basement membranes (distance <1 μm) was two-fold and three-fold higher, respectively, in the superficial and deep layers in OLP compared with NBM (P<0.001). The frequency distribution of mast cells associated with basal epithelium was not statistically different in both groups (P>0.05). The association of mast cells with laminin may be an important determinant of mast cell density in OLP. During OLP lesion formation and progression, the preferential distribution of mast cells in the immediate perivascular region provides an ideal situation for mast cell-derived mediators to influence the vascular endothelium.     

Granular cells in oral lichen planus

OBJECTIVE AND DESIGN: Three cases of granular cells associated with oral lichen planus (OLP) have been reported to date, which prompted us to look for the presence of granular cells in a consecutive series of 250 cases of OLP in the period 1996-1998. RESULTS: Only one case with granular cell changes was encountered in that series. H&E stained slides as well as direct immunofluorescence examination showed characteristics compatible with OLP. Part of the subepithelial connective tissue was replaced by a granular cell proliferation; S-100 protein was diffusely expressed in all granular cells, whereas no expression of smooth muscle actin was observed. CONCLUSION: Based on these findings it seems unlikely that the granular cells in the present case represent a so-called 'oral ceroid granuloma'. The presence of granular cells might rather have been a reactive phenomenon triggered by the inflammatory infiltrate or a granular cell tumour (GCT). Whether the simultaneous presence of a GCT and OLP in this particular case was based on a causal relationship or on coincidence still remains unknown.     

口腔扁平苔藓损害组织中树突状细胞亚群数量和比例

目的：研究口腔扁平苔藓（oral lichen planw,OLP）组织中树突状细胞（dendritic cell,DC）的亚群数量和比例,探索其在OLP疾病中的作用。方法：收集正常对照（HC组）,萎缩糜烂型OLP（E－OLP组）,斑纹型OLP（R－OLP组）的颊黏膜,通过流式细胞术染色和免疫组化染色,检测朗格汉斯细胞（CD1a＋CD11cint／lo CD207＋MHC II＋）、髓样DC （CD11c＋MHC II＋）、浆细胞样DC（CD11cint／lo CD123＋MHC II＋）和细胞毒性T细胞（CD3＋CD8＋）在组织中的浸润情况。结果：收集样本23例（HC组5例,E－OLP组7例,R－OLP组11例）,Bartlett检验各组数据方差不齐,采用Kruskal－Wallis非参数检验。朗格汉斯细胞的中位数比例分别为0．092％（HC）、0．564％（E－OLP）和0．541％（R－OLP）,3组间无统计学差异;髓样DC的中位数比例分别为0．311％（HC）、0．996％（E－OLP）和0．448％（R－OLP）,其中E－OLP组与HC组之间有统计学差异（P＜0．05）;浆细胞样DC的中位数比例分别为0．090％（HC）、3．490％（E－OLP）和2．010％（R－OLP）,2组OLP组与HC组之间均有统计学差异（P＜0．05）;CD8＋T细胞的中位数比例分别为0．126％（HC）、4．210％（E－OLP）和1．850％（R－OLP）,2组OLP组与HC组之间均有统计学差异（P＜0．05）。结论：DC在OLP中数量和比例增加,可能与疾病的自身免疫发病机制有关。     

Expression profile of chemokines and chemokine receptors in epithelial cell layers of oral lichen planus

BACKGROUND: To understand the immunopathological features of oral lichen planus (OLP), we analyzed the expression of chemokines in the epithelial cell layers. Methods: Epithelia from OLP or healthy gingiva were collected by laser microdissection. The chemokine and chemokine receptor expressions in the epithelia were analyzed by DNA microarray. RESULTS: High levels of MIP-3alpha/LARC/CCL20 and its receptor CCR6 were expressed in the lesional epithelia. Furthermore, DC-CK1/CCL18, ELC/CCL19, SDF-1/CXCL12 and CXCR4 expressions were also increased. Immunohistologial analysis showed that high numbers of Langerhans cells (LCs) were present in the epithelia of OLP. Lesional epithelia also expressed high levels of the ligands specific for CXCR3 (e.g. MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11) and CCR5 (e.g. RANTES/CCL5). CONCLUSIONS: Infiltration of LCs is orchestrated by CCR6. Further, LCs residing in the lesional epithelia may be a mature phenotype. Moreover, infiltration of T cells in OLP could be mediated by signaling pathways through CXCR3 and CCR5.     

The activation of Langerhans cells in oral lichen planus

The numbers of CD1, HLADR, HLADP and HLADQ positive, intraepithelial, dendritic cells were compared in lesions of oral lichen planus and normal oral mucosa using an immunoalkaline phosphatase technique. In normal mucosa, there were equal numbers of CD1 and HLADR positive cells but significantly fewer cells were positive for HLADP (P less than 0.001) and HLADQ (P less than 0.05). In lichen planus, the cells appeared more dendritic and equal numbers of CD1, HLADR, HLADP and HLADQ positive cells were found, with significantly more HLADP (P less than 0.01) and HLADQ (P less than 0.05) positive cells than in normal mucosa. There was no change in the number of CD1 and HLADR positive cells. These results show that although there is no change in the total number of Langerhans cells (CD1 positive cells) in lichen planus, there is an increase in Class II major histocompatibility antigen expression. This suggests that in lichen planus, Langerhans cells are immunologically active and play a role in lesion development.     

口腔白斑和扁平苔藓中TSGF的检测

目的 探讨恶性肿瘤特异性生长因（TSGF）的检测对口腔白斑和扁平苔藓的临床意义。方法 对45例鳞癌，12例白斑和32例扁平苔藓患者，测定其血中TSGF的浓度。结果 鳞癌的阳性率为53．33％，白斑为33．33％，扁平苔藓为25．00％。白斑与鳞癌的阳性率无显著性差异（P＞0．05）。扁平苔鲜与鳞癌的阳性率有显著性的差异（P＜0．05）。结论 检测患者血清中TSGF可做为临床预测口腔黏膜病是否有癌变倾向的初步手段。     

辅助性T淋巴细胞极化相关细胞因子在口腔扁平苔藓中的研究进展

口腔扁平苔藓是一种病因不明的皮肤黏膜慢性免疫炎症性疾病,辅助性T淋巴细胞(Thcell)在口腔扁平苔藓的发病机制中起到了重要作用。近年来,口腔扁平苔藓中Th细胞的极化状态引起了较为广泛的关注。研究表明,Th细胞极化相关细胞因子的变化与口腔扁平苔藓的发病密切相关。下文就这些细胞因子在口腔扁平苔藓中的研究进展作一综述。     

Psychological profile in oral lichen planus

AIM: Oral lichen planus (OLP) is an oral lesion with an enigmatic etiology. To explore the possibility of psycho-somatization, we evaluated the psychological personality profiles of OLP patients. METHODS: Twenty patients with reticular; 20 with erosive form of OLP, and 25 controls were tested with the psychological Minnesota Multiphasic Personality Inventory (MMPI)-202 test. Eight clinical scales (hypochondriasis, depression, hysteria, psychopathic deviate, paranoia, psychasthenia, schizophrenia, and hypomania) as well as cortisol level, CD3, CD4, CD8, and CD16 markers by group were compared. Psychosomatization was evaluated by the use of internalization ratio (IR) Index. RESULTS: A characteristic MMPI profile was noted in the OLP groups with high IR index value. Significant differences among the groups were detected for cortisol, CD4, CD8, and CD16 counts. Mean values for hypochondriasis, depression, and hysteria were all significantly different with significantly higher mean scores for both reticular and erosive OLP subjects compared with controls. CONCLUSIONS: Prolonged emotive stress in many OLP patients may lead to psychosomatization and may contribute to the initiation and clinical expression of this oral disorder. Clinical significance: If additional research involving a larger and more diverse sample of patients confirms these findings, clinical trials will be needed to determine whether adjunctive psychological intervention provides a benefit in treating patients with OLP.     

口腔扁平苔藓基因表达谱中差异表达基因初步探讨

目的筛选口腔扁平苔藓组织中的差异表达基因,并对其进行功能分类。方法用4 000种人类基因多聚酶链反应产物制成BiostarH- 40s型表达谱芯片,分离纯化正常口腔黏膜组织和口腔扁平苔藓病变组织mRNA,制备表达谱探针,用ScanArray 4000 荧光扫描仪扫描芯片荧光信号图像,分析正常口腔黏膜组织和口腔扁平苔藓组织之间差异表达的基因。结果1）在4 000条基因中,有213条基因表达差异,其中122条基因表达上调,91条基因表达下调。2）在表达上调基因中,功能分类主要包括免疫相关基因、代谢相关基因、癌基因、细胞因子、细胞信号和传递蛋白。3）在表达下调基因中,功能分类主要包括DNA结合、转录和转录因子、细胞信号和传递蛋白、免疫相关基因、细胞因子、代谢相关基因。结论口腔扁平苔藓的发生、发展过程中存在着多条不同功能基因表达调控的改变。     

Intra-epithelial subpopulations of T lymphocytes and Langerhans cells in oral lichen planus

This study has addressed the question of whether there is selective recruitment and distribution of intra-epithelial leucocytes in lesions of oral lichen planus (OLP). T-lymphocyte subsets were examined in the epithelium and peripheral blood of patients and controls using flow cytometry and double immunofluorescence, and the relationship between keratinocyte intercellular adhesion molecule-1 (ICAM-1) expression with T-lymphocyte and Langerhans cell (LC) distribution was examined. The circulating 'memory'subset (CD45RO⁺) of T-helper cells (CD4⁺) was increased from 49.1% in controls to 65.7% in patients ( P = 0.005), while the 'naive'subset (CD45RA⁺), which was absent from control epithelium, comprised 24% of helper cells in OLP ( P =0.037) and all T-cell and LC counts were significantly raised in ICAM-1-expressing areas of epithelium. These data demonstrate changes in intra-epithelial T-lymphocyte and LC populations compared with normal oral mucosa and suggest there is selective recruitment in OLP. In addition, Keratinocyte ICAM-1 expression does appear to be associated with accumulation of infiltrating T lymphocytes and LC.     

Immune mechanisms in oral lichen planus

Oral lichen planus (OLP) is a T cell-mediated inflammatory disease of the oral mucosa that has been extensively researched over many years but as yet the mechanisms of pathogenesis are still not fully understood. Whilst the specific aetiological factors driving OLP remain ambiguous, evidence points to the development of a chronic, dysregulated immune response to OLP-mediating antigens presented by innate immune cells and oral keratinocytes leading to increased cytokine, chemokine and adhesion molecule expression. These molecules recruit T cells and mast cells to the diseased site and orchestrate a complex interplay between cells that culminates in keratinocyte cell death, mucosal basement membrane destruction and long-term chronicity of the disease. The main lymphocytes involved are thought to be CD8+ cytotoxic and CD4+ Th1 polarised T cells although recent evidence indicates the involvement of other Th subsets such as Th9, Th17 and Tregs, suggesting that a more complex immune cell relationship exists during the disease process. This review provides an overview of the immune mechanisms at play in OLP pathogenesis with particular emphasis on the role of the different Th subsets and how these recent discoveries may guide research towards identifying potential therapeutic targets.     

OLP组织中Smad7蛋白的表达研究

目的:检测Smad7蛋白在口腔扁平苔藓(OLP)组织中的表达及分布,探讨其在OLP发病机制中的作用。方法:采用免疫组化SABC法,用Smad7兔抗人多克隆抗体检测60例OLP病变组织及10例正常口腔黏膜组织中Smad7蛋白的表达及分布。结果:Smad7在OLP病变组织有明显的阳性表达,而在正常口腔黏膜组织中阴性表达(P<0.05)。结论:Smad7蛋白在OLP病变组织中高表达,其在OLP发病机制中有重要作用。     

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口腔扁平苔藓(orallichenplanus,OLP)是一种累及口腔黏膜且可反复发作的慢性炎症疾病,患病率为0.51%,在口腔黏膜疾病中居第2位,属常见病。皮肤和黏膜可单独或同时发病,病理表现相似:主要以口腔黏膜不同程度的角化异常、基底层细胞液化变性、上皮下结缔组织中淋巴细胞呈带状浸润为典型表现。     

Th1 cytokines in oral lichen planus

BACKGROUND: Cell-mediated immune responses in oral lichen planus (OLP) may be regulated by cytokines and their receptors. METHODS: In situ cytokine expression and in vitro cytokine secretion in OLP were determined by immunohistochemistry and ELISA. RESULTS: The majority of subepithelial and intraepithelial mononuclear cells in OLP were CD8+. In some cases, intraepithelial CD8+ cells were adjacent to degenerating keratinocytes. CD4+ cells were observed mainly in the deep lamina propria with occasional CD4+ cells close to basal keratinocytes. Mononuclear cells expressed IFN-gamma in the superficial lamina propria and TNF-alpha adjacent to basal keratinocytes. Basal keratinocytes expressed TNF-alpha as a continuous band. TNF R1 was expressed by mononuclear cells and basal and suprabasal keratinocytes. There was variable expression of TGF-beta1 in the subepithelial infiltrate while all intraepithelial mononuclear cells were TGF-beta1-. Keratinocytes in OLP stained weakly for TGF-beta1. Unstimulated OLP lesional T cells secreted IFN-gamma in vitro. TNF-alpha stimulation down-regulated IFN-gamma secretion and up-regulated TNF-alpha secretion. IL-4, IL-10 and TGF-beta1 secretion were not detected. CONCLUSIONS: These data suggest the development of a T helper 1 immune response that may promote CD8+ cytotoxic T-cell activity in OLP.     

The frequency of Candida in oral lichen planus

ABSTRACT – Histologic material of typical lichen planus lesions from 43 patients was studied. Two sections of each specimen were stained with hematoxylin-eosin and 10 sections by the PAS method. Only 1 of 43 biopsies was invaded by Candida, and hyphae were present in all of the 10 PAS-stained sections of this case. The results show that oral lichen planus has a considerably lesser susceptibility than oral leukoplakia to invasion by Candida albicans.     

微小RNA在口腔扁平苔藓中的作用

微小RNA家族在调控基因表达中的重要作用日益受到关注,其调控的基因涉及细胞增殖、凋亡、生长、分化和代谢、血管化和免疫应答等多种生物过程,其表达谱和表达量的变化与多种疾病如肿瘤、炎症性疾病、自身免疫性疾病的发生、发展密切相关.本文对口腔扁平苔藓中微小RNA的研究现状作一综述.     

Pathogenesis of oral lichen planus – a review

J Oral Pathol Med (2010) 39 : 729–734 Oral lichen planus (OLP) is a T‐cell‐mediated chronic inflammatory oral mucosal disease of unknown etiology. OLP presents as white striations, white papules, white plaques, erythema, erosions, or blisters affecting predominantly the buccal mucosa, tongue and gingiva. Both antigen‐specific and non‐specific mechanisms are hypothesized to be involved in the pathogenesis of oral lichen planus (OLP). Antigen‐specific mechanisms in OLP include antigen presentation by basal keratinocytes and antigen‐specific keratinocyte killing by CD8⁺ cytotoxic T cells. Non‐specific mechanisms include mast cell degranulation and matrix metalloproteinase activation in OLP lesions. These mechanisms may combine to cause T cell accumulation in the superficial lamina propria, basement membrane disruption, intra‐epithelial T cell migration and keratinocyte apoptosis in OLP. The various hypotheses proposed for pathogenesis of oral lichen planus are discussed in this review.     

口腔扁平苔藓实验模型建立的研究进展

口腔扁平苔藓是一种最常见的口腔黏膜慢性炎症性疾病,临床上缺乏有效的治疗措施。寻找和建立合适的实验模型对开展口腔扁平苔藓诊治研究有着重要的意义,但因口腔扁平苔藓的发病原因和机制未明,给实验模型的建立带来困难,是目前口腔学者面临的难题之一。迄今为止,国内外尚未建立完善的口腔扁平苔藓动物模型,而相关细胞模型已较为成熟,本文就目前口腔扁平苔藓实验模型的研究进展进行综述。