Lichen Planus Cell Research Articles

Comparative Evaluation of Mast Cells in Lichen Planus and Oral Lichenoid Reaction with Giemsa Staining

Introduction: Lichen planus is a relatively common and chronic mucocutaneous disease with unknown. Oral lichenoid reaction is clinical and histopathological similar to lichen planus, but the cause of it is different. Mast cells are responsible for the accumulation of inflammatory cells in the connective tissue. The aim of study was evaluation of the role of mast cells in pathogenesis of two groups of lesions.
 Methods: This cross-sectional study was performed on 26 samples of oral lichen planus, oral lichenoid reaction lesions and 5 samples of irritation fibroma. After the staining with the Giemsa, sections were observed under the optical microscope (x400), and the number of mast cells was counted. The results were analyzed using the SPSS16 software, T test, Mann- Whitney and Chi-squared statistical tests.
 Results: The total number of mast cells and degranulated mast cells in two groups were significantly higher than the control group (P<0/05). Nevertheless, the total number of mast cells, the number of degranulated mast cells and the ratio of degranulated mast cells to the total mast cells had no significant difference between the two groups of lesions. (P> 0/05).
 Conclusion: Mast cells play a role in the pathogenesis of lichen planus and lichenoid reaction lesions. The number of degranulated mast cells and the ratio of degranulated to the total mast cells cannot help to differentiate these two groups of lesions. Clinical examinations and proper history and attention to their etiologic factors have a significant role in differentiating them.

Skin-infiltrating T cells display distinct inflammatory signatures in lichen planus, bullous pemphigoid and pemphigus vulgaris.

We here thought to dissect the inflammatory signature in lesions of three skin disorders, which show a common adaptive immune response against autoantigens of the skin but are characterized by diverging clinical phenotypes. Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are type-2-dependent, IgG autoantibody-driven blistering disorders of mucous membranes and skin, which target desmoglein (Dsg)3 and bullous pemphigoid (BP)180, respectively. In contrast, lichen planus (LP) is a common chronic inflammatory disease of the skin and mucous membranes with a pronounced dermal T cell infiltrate. We previously identified peripheral type 1 and 17 T cell responses against Dsg3 and BP180 in a cohort of LP patients strongly suggesting that the underlying inflammatory T cell signature may drive the evolving phenotype. Paraffin-embedded skin biopsies from well-characterized patients with LP (n=31), BP (n=19), PV (n=9), and pemphigus foliaceus (PF) (n=2) were analysed. Areas with the most prominent inflammatory infiltrate were excised with punch biopsies and tissue microarrays (TMA) containing multiple biopsies were created. Using multicolor immunofluorescence, the inflammatory infiltrate was stained with antibodies against multiple cellular markers, i. e. CD3ϵ, CD4, CD15, TCR-δ, the cytokine IL-17A, and the transcription factors, T-bet and GATA-3. In LP, there was a higher number of CD4+ T cells expressing T-bet compared to GATA-3. In contrast, CD4+ T cells in PV and BP skin lesions more frequently expressed GATA-3 than T-bet. IL-17A+ cells and IL-17A+ T cells were found to a similar extent in all the three disorders. IL-17A+ granulocytes were more predominant in BP than in LP or PV. Of note, the majority of IL-17A+ cells in LP were neither T cells nor granulocytes. Our findings in inflammatory skin infiltrates clearly show a predominant type 1 signature in LP in contrast to a preponderance of type 2 T cells in PV and BP. In contrast to LP, granulocytes and to a much lesser extent CD3+ T cells were a cellular source of IL-17A in BP and PV. These data strongly suggest that different inflammatory cell signatures drive evolving clinically diverse phenotypes of LP, PV and BP despite common target antigens of the skin.

Subset of CD8+ and FOXP3 + T cells in lichen planus associated with chronic hepatitis C infection.

To verify whether there are differences between populations of CD8+and FoxP3+T cells in lesions of oral lichen planus associated with hepatitis C virus chronic infection (OLP-HCV) and lesions of idiopathic oral lichen planus (OLP-I). A case-control study was performed using a convenience sample of 11 paraffin-embedded tissue blocks of OLP-HCV and 19 of OLP-I. Histological sections stained with haematoxylin and eosin were used to classify the intensity of inflammatory infiltrate. Immunohistochemistry was used to identify CD8+and FoxP3+T cells. The count of positive cells was compared between the two groups and correlated to clinical and demographic data (p<0.05). There were no statistically significant differences in the distribution of CD8+and FoxP3+T cells regarding the inflammatory infiltrate in lesions of OLP-HCV and OLP-I. Atrophic/erosive lesions showed a higher relationship between counts of CD8/FoxP3 T cells per mm2 (p=0.018) and counts of CD8+T cells per mm2 (p=0.034) in OLP-HCV group compared to OLP-I group. Overall, no difference was found between cell populations in the lesions of OLP-HCV and OLP-I. However, atrophic/erosive lesions of OLP-HCV had a higher amount of CD8+T cells and lower FoxP3 expression.

Memory T Cells (CD45RO) Role and Evaluation in Pathogenesis of Lichen Planus and Lichenoid Mucositis.

Memory T cells have the ability to survive in a quiescent state for longer periods and are responsible for the rapid responses on subsequent exposure to antigen. Analyzing memory T cells in Oral Lichen planus (OLP) and Lichenoid Mucositis (LM) suggest that these cells may play a role in the immunopathogenic mechanisms. To identify and evaluate Memory T cells in Lichen Planus (LP), Lichenoid Mucositis (LM) and Normal Mucosa (NM) using CD45RO monoclonal antibody immunohistochemically. A total of 30 cases (15 cases of OLP and 15 cases of LM) clinically and histopathologically diagnosed, and 10 cases of NM were stained for CD45RO monoclonal antibody, immunohistochemically using Biotin Streptavidin method. Staining intensity of CD45RO expression was statistically analysed using Chi-square Test. The present study demonstrated a higher expression of CD45RO in connective tissue layer of OLP (53.3% intense staining) when compared to LM (20% intense staining) and no intense staining in NM. The difference in staining intensity pattern between the study groups was statistically significant (p=0.014). This study demonstrates a statistically significant rise in memory T cells in LP than in LM, indicating the possible different immunopathogenic mechanisms.

Activation of myeloid dendritic cells, effector cells and regulatory T cells in lichen planus.

BackgroundLichen planus (LP) is a chronic mucocutaneous inflammatory disease. Evaluating the balance between regulatory T cells and effector T cells could be useful for monitoring the proinflammatory profile of LP. Therefore, this study aimed to assess populations of dendritic cells (DCs) and regulatory and effector T cells in peripheral blood samples collected from patients with LP to evaluate the polyfunctionality of T cells upon toll-like receptor (TLR) activation.MethodsPeripheral blood mononuclear cells collected from 18 patients with LP and 22 healthy control subjects were stimulated with agonists of TLR4, TLR7, TLR7/TLR8 or TLR9. Frequencies of circulating IFN-α+ plasmacytoid DCs (pDCs); TNF-α+ myeloid DCs (mDCs); regulatory T cells (Tregs); and IL-17-, IL-10-, IL-22-, TNF-, and IFN-γ-secreting T cells were assessed via flow cytometry.ResultsThe frequencies of regulatory CD4+ and CD8+CD25+Foxp3+CD127low/− T cells and TNF-α+ mDCs were induced following activation with TLR4, TLR7 and TLR8 agonists in the LP group. Moreover, increased baseline frequencies of CD4+IL-10+ T cells and CD8+IL-22+ or IFN-γ+T cells were found. In the LP group, TLR4 activation induced an increased frequency of CD4+IFN-γ+ T cells, while TLR7/8 and staphylococcal enterotoxin B (SEB) activation induced an increased frequency of CD8+ IL-22+ T cells. An increased frequency of polyfunctional CD4+ T cells that simultaneously secreted 3 of the evaluated cytokines (not including IL-10) was verified upon TLR7/8/9 activation, while polyfunctional CD8+ T cells were already detectable at baseline.ConclusionsTLR-mediated activation of the innate immune response induced the production of proinflammatory mDCs, Tregs and polyfunctional T cells in patients with LP. Therefore, TLR activation has an adjuvant role in inducing both innate and adaptive immune responses.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0938-1) contains supplementary material, which is available to authorized users.

Up-regulation of Proinflammatory Genes and Cytokines Induced by S100A8 in CD8+ T Cells in Lichen Planus.

Lichen planus (LP) is a chronic inflammatory mucocutaneous disease. The inflammatory status of LP may be related to S100A8 (myeloid-related protein 8; MRP8) activation of cytotoxic cells. The aims of this study were to evaluate S100A8 expression in skin lesions and the in vitro effects of S100A8 on CD8+ T cells and natural killer (NK) cells in LP. Increased levels of S100A8/S100A9 were detected in the skin lesions as well as in the sera of subjects with LP. S100A8 expression induced an increased cytotoxic response by peripheral blood CD8+CD107a+ T cells as well as by NK CD56bright cells in patients with LP. Increased expression of interleukin (IL)-1β, tumour necrosis factor (TNF) and IL-6 in the CD8+ T cells of patients with LP was induced by S100A8, in contrast to the control group that produced IL- 10 and interferon (IFN) type I genes. These data suggest that, in individuals with LP, S100A8 may exert distinct immunomodulatory and cytotoxicity functions.

Langerhans cells in lichen planus and lichenoid mucositis an immunohistochemical study.

Aim:The aim of this study is to identify and evaluate Langerhans cell (LC) in lichen planus (LP), lichenoid mucositis (LM) and normal mucosa (NM) using CD1a monoclonal antibody immunohistochemically.Materials and Methods:A total of 15 cases of oral lichen planus and 15 cases of LM were selected based on clinical examination and confirmed by histopathological analysis. The biopsies from the 10 patients were taken from normal buccal mucosa as control. Paraffin blocks of tissue were made, which are used for routine hematoxylin and eosin staining and immunohistochemical staining using biotin streptavidin methods (CD1a monoclonal antibody). Analysis of CD1a expression was performed by evaluating the labeling index (LI) for each slide.Results:The mean CD1a LI for LP was significantly higher than that of LM and NM in the basal and supra basal layer. The mean CD1a positive cells in the connective tissues for LP were higher than that of LM and NM.Conclusion:This study clearly demonstrates a statistically significant increase in number of LC in LP than in LM, indicating the possible different immunopathogenic mechanisms.

Quantitative Score of Langerhans Cells in Lichen Planus and Amalgam Lichenoid Reaction

Quantitative Score of Langerhans Cells in Lichen Planus and Amalgam Lichenoid Reaction

Expression of Foxp3 and interleukin-17 in lichen planus lesions with emphasis on difference in oral and cutaneous variants

Foxp3 is a specific marker for regulatory T cells (Tregs), and interleukin (IL)-17 is the signature cytokine of T-helper (Th) 17 cells. Recent studies suggested that Foxp3+ Tregs and IL-17+ Th17 cells may be involved in pathogenesis of lichen planus (LP). The objectives of this study were to examine the immunoexpression of Foxp3 and IL-17 in archival paraffin-embedded biopsy specimens from 80 cases of LP (oral LP, n=42; cutaneous LP, n=38) and compare against normal control tissues (oral mucosa, n=10; skin, n=10). The results showed that the mean number of Foxp3 and IL-17 expression in LP was significantly higher compared to controls, respectively (both P<0.001). A positive correlation between Foxp3 and IL-17 expression (r=0.273; P=0.014) was observed. Moreover, the mean number of Foxp3 expression in oral LP was significantly higher than cutaneous LP (P<0.001). Collectively, our findings demonstrated the increased expression of Foxp3 and IL-17 in LP lesions including oral and cutaneous variants. Foxp3 expressing in oral LP was higher than cutaneous LP, which may be associated with the difference in clinical behaviour of the two variants of the disease. Further studies are required to investigate the immunopathologic mechanisms and therapeutic target of Foxp3+ Tregs and IL-17+ Th17 cells in LP.

Indoleamine 2,3-Dioxygenase (IDO): The Antagonist of Type I Interferon-Driven Skin Inflammation?

Recent studies have provided evidence that a type I interferon (IFN)-driven immune response might play an important role in the pathogenesis of lichen planus (LP), an inflammatory disorder of the skin of unclear etiology. Plasmacytoid dendritic cells in affected skin from LP have been proposed to produce IFN-alpha/beta locally, which leads to the expression of IFN-inducible chemokines such as IP10/CXCL10 in the epidermis. This chemokine recruits chemokine receptor CXCR3-expressing T-lymphocytes into the skin via CXCR3/IP10 interactions. Indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan and suppresses T-cell proliferation, is induced by IFNs and other inflammatory cytokines. We show that type I IFN-mediated skin disorders, such as LP, strongly express IDO in lesional skin. This expression closely correlates to the expression of the highly specific type I IFN marker MxA. We further demonstrate that the IDO+ cells in LP are large myeloid CD11c+S100+CD68(-) dendritic cells. Accordingly, CD11c+ antigen-presenting cells significantly up-regulate IDO gene expression and intracellular IDO protein expression after stimulation with IFN-alpha in vitro. These findings reveal that both proinflammatory and counterregulatory mechanisms are operative in cutaneous lesions of LP. We propose that the balance of these mechanisms may be involved in the pathogenesis of this disorder.

A quantitative assessment of Langerhans cells in oral mucosal lichen planus and leukoplakia.

Quantitative analysis of Langerhans cells stained with OKT6 in the epithelium of 42 patients with oral mucosal lichen planus and 14 patients with oral mucosal leukoplakia showed significantly greater numbers of Langerhans cells in lichen planus. This may reflect the role of Langerhans cells in the pathogenesis of this condition and their identification could help in distinguishing lichen planus from leukoplakia.

Half-and-half cells in lichen planus

In the course of a study of wound healing in four patients with lichen planus, we found transformed keratinocytes with a hitherto undescribed ultrastructure in both wounded and undisturbed papules. We have called these epidermal cells half-and-half cells because they showed changes on the one hand of increased synthetic activity and, on the other hand, of fibrillar transformation closely resembling that seen in fully developed colloid bodies. We suggest that these half-and-half cells may provide a useful clue to the early changes occurring in colloid body formation.

Presence of Human β-Defensin-2 in Oral Lichen Planus and its Histamine Releasing Effect

Objective: To determine by immunohistochemical means the localization of human β-defensin-2, a peptide with antimicrobial activity, in oral lichen planus. The release of histamine from mast cells elicited by human β-defensin-2 was also investigated.Materials and Methods: Biopsy specimens of oral lichen planus, synthetic human β-defensin-2, human α-defensin-1, and mast cells isolated from Sprague Dawley rats were used. Tissue sections were embedded in paraffin and immunostained by the streptavidin-biotin-coupled peroxidase method. Isolated rat mast cells were injected with synthetic human β-defensin-2 and human α-defensin-1. Evans blue dye was injected into the tail vein of Sprague Dawley rats, followed by various doses of histamine, human β-defensin-2, human α- defensin-1, and saline.Results: Epithelial cells in lichen planus from the corneal layer to the spinous layer, were positively stained with anti-human β-defensin-2 antibody. Mast cells in subepithelial areas were also stained by anti-human β-defensin-2 antibody. Human β-defensin-2-induced histamine release from the isolated rat mast cells occurs in a dose-dependent manner. When human β-defensin-2 was injected into rat skin intradermally, the vascular permeability increased. These responses were completely abolished upon injection of the antihistamine drug diphenhydramine hydrochloride.Conclusion: Human β-defensin-2 and histamine may play an important role in the formation of oral lichen planus.

Killer cell immunoglobulin-like receptor expression delineates in situ Sézary syndrome lymphocytes.

p140/KIR3DL2 has been identified in malignant cell lines isolated from the skin and blood of patients with transformed mycosis fungoides (MF) and Sézary's syndrome (SS). For the first time, the expression of a cell membrane structure appeared to be able to distinguish CD4+ tumour lymphocytes from reactive lymphocytes in these small cutaneous T-cell lymphomas (CTCLs). This study has examined the in vivo expression of this receptor in various CTCL subtypes, which constituted a heterogeneous group. Tumour cells diffusely expressed KIR in SS, in lymphomatoid papulosis (LyP) and in CD4+CD30+ as well as CD8+ large cell pleomorphic CTCL. In contrast, the infiltrating lymphocytes did not express KIR in MF at the patch/plaque stage or in CD4+CD30- large cell pleomorphic CTCL, except for scattered small cells. One quarter of the transformed MF tested exhibited KIR+ tumour cells, suggesting heterogeneity in this subtype. KIR expression was also examined in inflammatory lesions characterized by a dense infiltrate of T cells, such as lupus erythematosus and lichen planus. Only scattered CD8+ cells in lichen planus expressed a significant amount of KIR3DL2. Taken together, these results show for the first time that KIR molecules are expressed in distinct subtypes of malignant CTCL. It is also shown for the first time that SS and MF, which are frequent variants of CTCL with similar histological features, can be distinguished by their KIR3DL2 expression analysis. The identification of this KIR also differentiates between lupus erythematosus and lichen planus, which are both diseases with dense benign lymphocytic infiltrates.

Cellular localization of fractalkine at sites of inflammation: antigen-presenting cells in psoriasis express high levels of fractalkine.

Chemokines play a key role in cell trafficking at sites of inflammation. The fractalkine CX3C chemokine is unique in several aspects. Fractalkine is expressed on activated endothelial cells and exists in two forms, either membrane anchored or in a soluble form. The soluble form is a potent chemotactic agent for T cells/monocytes and the anchored form functions as an adhesion molecule. In view of these specific functions fractalkine is capable of controlling the key regulatory mechanisms of cell trafficking at sites of inflammation. Little is known about the significance of this important molecule in inflammatory diseases. We undertook this study to elucidate the role of fractalkine in inflammatory diseases of the skin. We used a polyclonal antifractalkine antibody (immunoperoxidase and immunofluorescence stainings) in cryosections obtained from tissues of normal skin and that of selected cutaneous inflammatory diseases (psoriasis, lichen planus, eczema). Increased expression of fractalkine was observed in the dermal blood vessels of lichen planus, eczema and psoriasis tissues. The most striking finding was that the dermal dendrocytes in the papillary dermis of psoriasis tissues expressed high levels of fractalkine. Compared with 186.64 +/- 51.69 fractalkine positive dermal dendrocytes per mm2 of the upper dermis of psoriatic tissue, the number of positive cells in lichen planus, eczema, and normal skin were 17.29 +/- 12.50, 12.50 +/- 6.75 and 5.93 +/- 3.53, respectively. We also performed double label immunofluorescence staining with nerve growth factor receptor (NGF-R) antibody and fractalkine antibody. NGF-R-positive terminal cutaneous nerves were in close contact with the fractalkine-positive dermal dendrocytes in psoriatic lesions. The results of this study confirm that fractalkine is upregulated at sites of inflammation. Thus, it is likely that this molecule plays a key part in cell trafficking. An increased expression of fractalkine at the dermal papillae provides a plausible explanation for the migration and accumulation of T cells at these sites in psoriasis. Earlier studies have reported an increased number of dermal dendrocytes in psoriatic tissue; however, the functional role of these cells in the pathogenesis of psoriasis is largely unknown. Expression of fractalkine on the surface of dermal dendrocytes suggests an active role for these cells in localization and activation of lesional T cells.

Detection of clonal T cells in lichen planus.

Detection of clonal T cells in lichen planus.

Fine structure and cellular contacts of Langerhans cells in lichen planus

Fine structure and cellular contacts of Langerhans cells in lichen planus

Langerhans cells expressing HLA-DQ, HLA-DR and T6 antigens in normal oral mucosa and lichen planus.

We compared Langerhans cells (LC) expressing HLA-DQ, HLA-DR and T6 antigens in biopsies from the same oral mucosal site in 12 patients with oral lichen planus and eight healthy volunteers. LC expressing each antigen were observed in all the specimens, but in lichen planus the cells were located in higher levels of the epithelium than in controls. Compared with controls, lichen planus contained significantly more HLA-DQ-positive LC (P = 0.04) and fewer HLA-DR-positive LC (P = 0.05), but there was no such difference in T6-positive LC. In lichen planus specimens, there were significantly more LC expressing HLA-DQ and T6 than HLA-DR (P = 0.0001 and 0.02 respectively); no such differences were found in normal mucosa. Epithelial cells in lichen planus expressed HLA-DR antigen, but not HLA-DQ or T6 antigens. We conclude that in lichen planus there is modulation of HLA-DR and HLA-DQ antigen expression by LC, or differences in the number of LC expressing those antigens.

Lichen planus: evaluation of cells in skin lesions and of T-lymphocyte subsets in blood.

ABSTRACTThe purpose of the present study was to examine the phenotype of cutaneous immunocompetent cells and to quantify Langerhans cells in Lichen planus by the use of monoclonal antibodies directed against T‐cell populations.Helper cells (OKT4+) and Suppressor/cytotoxic cells (OKT8+) were observed in all cutaneous infiltrates, and numerous Langerhans cells were identified by OKT6, BL6, and BL2 (HLA‐DR) in the epidermis and dermis.The quantification of Langerhans cells demonstrated that the number of dendritic cells in epidermis is greater in involved skin than in non‐involved skin. In recent lesions, Langerhans cells are more abundant than in older lesions.The results in peripheral blood indicated a T Helper/Suppressor imbalance with a decreased T‐Suppressor/cytotoxic subpopulation in patients with lichen planus diseases.In lichen planus, our results suggest an immunological reaction involving all the immunocompetent cell subpopulations with a first stage of information by Langerhans cells (OKT6+, BL6+, BL2+ (HLA‐DR)) and Helper cells (OKT4+), and second stage mediated by Suppressor/cytotoxic cells (OKT8+).

In situ identification of mononuclear cells in lichen planus.

In this study, the in situ immunological typing of cell populations in lichen planus was attempted. T lymphocytes and suppressor/cytotoxic subsets, B lymphocytes, macrophages, immunocytes and Langerhans' cells were studied by one or more technical parameters and semiquantitative assessment of T cell populations were carried out. A critical evaluation of assays for T cell characterization was also attempted. T cells were found predominant in lichen planus infiltrate but macrophages were also many. Langerhans' cells were increased in the epidermis compared to normal skin and contact dermatitis.