Pathogenesis Of Oral Lichen Planus Research Articles

PA28γ induces dendritic cell maturation and activates T-cell immune responses in oral lichen planus.

Oral lichen planus (OLP) is a common chronic inflammatory disease of the oral mucosa, the mechanism of its inflammatory progression has not yet been fully elucidated. PA28γ plays a significant role in a variety of immune-related diseases. However, the exact role of PA28γ in the pathogenesis of OLP remains unclear. Here, we demonstrated that PA28γ is overexpressed in epithelial cells and inflammatory cells of OLP tissues but has no significant relationship with OLP subtypes. Functionally, keratinocytes with high PA28γ expression could induce dendritic cell (DC) maturation and promote the T-cell differentiation into Th1 cells in response to the immune response. In addition, we found that a high level of PA28γ expression is associated with high numbers of infiltrating mature DCs and activated T-cells in OLP tissues. Mechanistically, keratinocytes with high PA28γ expression could promote the secretion of C-C motif chemokine (CCL)5, blocking CCL5 or/and its receptor CD44 could inhibit the induction of T-cell differentiation by keratinocytes with high PA28γ expression. In conclusion, we reveal that keratinocytes with high expression of PA28γ in OLP can induce DC maturation and promote T-cell differentiation through the CCL5-CD44 pathway, providing previously unidentified mechanistic insights into the mechanism of inflammatory progression in OLP.

Streptococcus salivarius ameliorates the destructive effect on the epithelial barrier by inhibiting the growth of Prevotella melaninogenica via metabolic acid production.

Oral lichen planus (OLP) is one of the most common oral mucosal diseases, exhibiting a higher prevalence in women than men, but its pathogenesis is still unclear. Current research suggests that microbial dysbiosis may play an important role in the pathogenesis of OLP. Our previous research has found that the increase of Prevotella melaninogenica and decrease of Streptococcus salivarius have been identified as a potential pathogenic factor in OLP. Consequently, the objective of this study is to examine whether S. salivarius can counteract the detrimental effects of P. melaninogenica on the integrity of the epithelial barrier function. Epithelial barrier disruption was induced by P. melaninogenica in human keratinocytes (HaCaT cells). HaCaT cells were pretreated with S. salivarius(MOI=20) or cell-free supernatant for 3h, followed by treatment with P. melaninogenica (MOI=5) for 3h. The epithelial barrier integrity of HaCaT cells was detected by FD4 permeability. The mRNA level of tight junction protein was detected by quantitative real-time polymerase chain reaction (PCR). Immunofluorescence and Western Blot were used to detect the protein expression of zonula occludin-1 (ZO-1). The serial dilution-spotting assay was applied to monitor the viability of P. melaninogenica at the end of 8 and 24h incubation. Challenge by P. melaninogenica decreased the levels of tight junction proteins, including occludin, ZO-1, and claudin in HaCaT cells. S. salivarius or its cell-free supernatant inhibited the down-regulation of ZO-1 mRNA and protein expression levels induced by P. melaninogenica and thus improved the epithelial barrier function. The inhibitory effect of the cell-free supernatant of S. salivarius on the growth of P. melaninogenica is associated with metabolic acid production rather than with bacteriocins and hydrogen peroxide. These results suggest that live S. salivarius or its cell-free supernatant significantly ameliorated the disruption of epithelial tight junctions induced by P. melaninogenica, likely through the inhibition of P. melaninogenica growth mediated by metabolic acid production.

Evaluation of the Role of Oral Microbes in Pathogenesis of Oral Lichen Planus

ABSTRACT Background: The pathophysiology and etiology of oral lichen planus (OLP) are still unknown, despite the fact that the condition’s progression has been connected to a T-cell-based immune response. Research has focused on variables, such as oral bacteria, that may cause an autoimmune reaction with conflicting results. Aim: This study was conducted to evaluate the role of oral microorganisms in the pathogenesis of OLP. Materials and Methods: In this study, 82 formalin-fixed paraffin-embedded specimens of histopathologically confirmed cases of OLP and 20 such specimens of normal healthy subjects were obtained. Immunohistochemistry was carried out for the identification of microorganisms. Results: Candida albicans was observed in 47.12% of OLP cases and 9.43% of healthy controls. Helicobacter pylori was discovered in 45.21% of OLP cases and 13.46% of healthy controls. Periodontopathogenic bacteria was found in 33.14% of OLP cases and 13.45% of healthy controls. Human papillomavirus (HPV)-16 was noticed in 38.12% of OLP cases and 11.24% in the control group. HPV-18 was found in 32.43% of OLP patients and 11.43% in the control group. Mycoplasma salivarium was found in 46.47% of OLP patients and 6.45% in control. Conclusion: It was observed that several microorganisms like H. pylori, C. albicans, M. salivarium, periodontopathogenic bacteria, HPV-16, and HPV-18 were found to be related to OLP.

Microbial Profiles in Oral Lichen Planus: Comparisons with Healthy Controls and Erosive vs. Non-Erosive Subtypes.

Recent studies have begun exploring the potential involvement of microbiota in the pathogenesis of oral lichen planus (OLP), yet comprehensive investigations remain limited. Hence, this study aimed to compare the microbial profiles in saliva samples obtained from patients with OLP against those from healthy controls (HC), along with a comparison between erosive (E) and non-erosive (NE) OLP patients. Saliva samples were collected from 60 OLP patients (E: n = 25, NE: n = 35) and 30 HC individuals. Analysis revealed no significant differences in alpha diversity, as assessed by the Chao1 and Shannon index, across the three groups. However, Bray-Curtis distance analysis indicated a significant disparity in microbiome composition distribution between HC and E-OLP, as well as HC and NE-OLP groups. The six most abundant phyla observed across the groups were Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Fusobacteria, and Saccharibacteria (TM7). Notably, OLP groups exhibited a higher prevalence of Bacteroidetes. Prevotella emerged as the predominant genus in the OLP groups, while Capnocytophaga showed a relatively higher prevalence in E-OLP compared to NE-OLP. This study's findings indicate a notable difference in microbiota composition between HC and patients with OLP. Additionally, differences in the microbiome were identified between the E-OLP and NE-OLP groups. The increase in the proportion of certain bacterial species in the oral microbiome suggests that they may exacerbate the inflammatory response and act as antigens for OLP.

TYK2 inhibition with deucravacitinib ameliorates erosive oral lichen planus.

Erosive oral lichen planus (OLP) is a challenging disease. This T cell driven disorder frequently shows a treatment unresponsive course and strongly limits patients' quality of life. The disease lacks FDA or EMA approved drugs for its treatment and the efficacy of the commonly administered treatments (i.e. topical and systemic steroids, steroid sparing agents) is often only partial. Although the etiopathogenesis of the disease still needs to be fully elucidated, recent advances helped to identify interferon-ɣ (IFN-ɣ) as a pivotal cytokine in OLP pathogenesis, thus making the interference with its signalling a therapeutic target. Janus kinase (JAK) inhibitors therefore gained relevance for their inhibitory effect on IFN-ɣ signalling. While some drugs such as abrocitinib, upadacitinib, tofacitinib directly interfere with IFN-ɣ signalling through blockade of JAK1 and/or JAK2, deucravacitinib, a selective TYK-2 inhibitor indirectly interferes on IFN-ɣ activation through interference with interleukin (IL)-12, a potent promotor for Th1/IFN-ɣ responses. This mechanism of action makes deucravacitinib a candidate drug for the treatment of OLP. Here we provide initial evidence that deucravacitinib 6 mg daily has a beneficial effect in three patients with oral OLP.

Studying the relationship between oral lichen planus and periodontal disease: Value on periodontal pathogens and oral hygiene

BACKGROUND: Oral lichen planus is a chronic inflammatory condition of the oral mucosa characterized by white, lacy lesions. The etiology of oral lichen planus is complex and remains unclear, but it is thought to be a T-cell mediated autoimmune disease. Several factors have been implicated in the pathogenesis of oral lichen planus, including genetic predisposition, dental materials, iatrogenic factors, infections, autoimmunity, and bowel disease. The microflora of the oral cavity plays an important role in maintaining oral health and preventing disease. However, its role in the development and progression of oral lichen planus is not yet totally understood. Some studies have shown that there are differences in the microflora of oral lichen planus patients compared to healthy controls. These differences may be related to the inflammatory process in oral lichen planus, or they may be a contributing factor to the disease.
 AIM: Identify the prevalence of the detection of periodontopathogenic microorganisms in oral lichen planus patients and compare their prevalence in healthy non-oral lichen planus patients.
 MATERIALS AND METHODS: A cross-sectional, single-center study was conducted. A total of 75 patients were recruited, 45 with oral lichen planus and 30 healthy controls. The groups were formed by simple random sampling. The diagnosis of oral lichen planus was confirmed histologically in the main group. The forms and localization of oral lichen planus were determined in the main group based on clinical examination. In the control group, patients were divided into two subgroups depending on the presence of chronic periodontitis or gingivitis. The prevalence of periodontal pathogens was assessed based on the analysis of culture results. Among the 48 bacteria isolated from the oral mucosa of the affected site in the main and control groups, we focused on the microbiota of only periodontal bacteria to study their role and assess their impact on disease progression.
 RESULTS: Among the 45 patients with a clinical diagnosis of oral lichen planus, there were 10 (22.22%) men and 35 (77.78%) women, with a mean age of 55.3±13.4 years. The control group included 30 healthy volunteers, 8 (26.67%) men and 22 (73.33%) women, with a mean age of 54.8±12.7 years. In patients with oral lichen planus regardless of their periodontal status the percentage of seropositivity for A. actinomycetemcomitans, V. parvula, P. gingivalis, T. denticola is higher compared to their healthy counterparts with gingivitis and periodontitis.
 CONCLUSION: The study found an increased frequency of detection of pathogenic microorganisms, such as A. actinomycetemcomitans, V. parvula, P. gingivalis, and T. denticola, in patients with oral lichen planus, regardless of the presence of periodontitis. These periodontopathogens may be associated with oral lichen planus. However, further studies are needed to clarify their role in the pathogenesis of the disease.

Inflammatory cytokines and oral lichen planus: a Mendelian randomization study.

Inflammatory cytokines have long been considered closely related to the development of oral lichen planus (OLP), and we further explored the causal relationship between the two by Mendelian randomization (MR) method. We performed bidirectional MR analyses by large genome-wide association studies (GWAS). The data included a large-scale OLP dataset, as well as datasets of 41 inflammatory cytokines. All data were obtained from the University of Bristol database, which includes 41 inflammatory cytokines, and the GWAS Catalog database, which includes 91 inflammatory cytokines. OLP data were obtained from the Finngen database, which includes 6411 cases and 405770 healthy controls. We used the inverse variance weighted (IVW) method, MR-Egger method, weighted median method, simple mode method and weighted mode method to analyze the causal relationship between inflammatory cytokines and OLP, and we also combined with sensitivity analysis to further verify the robustness of the results. We performed a meta-analysis of positive or potentially positive results for the same genes to confirm the reliability of the final results. We primarily used the IVW analysis method, corrected using the Benjamin Hochberg (BH) method. When p<0.00038 (0.05/132), the results are significantly causal; when 0.00038<p<0.05, the results are potentially causal. We found a total of 7 inflammatory cytokines with significant or potential associations with OLP (University of Bristol database: 2, GWAS Catalog database: 5). In the reverse analysis, we found that a total of 30 inflammatory cytokines were significantly or potentially associated with OLP (University of Bristol database: 5, GWAS Catalog database: 25). After sensitivity analysis and meta-analysis, we finally determined that there was a causal relationship between a total of 3 inflammatory cytokines and OLP in the forward analysis, the most significant of which was FGF21 (p=0.02954, odds ratio (OR): 1.113, 95% confidence interval (95%CI): 1.011-1.226). In the reverse analysis, 14 inflammatory cytokines were causally associated with OLP, the most significant of which was PLAU (p=0.00002, OR: 0.951, 95%CI: 0.930-0.973). There is a causal association between OLP and some inflammatory cytokines, which may play an important role in the pathogenesis of OLP and require further attention.

Pathogenesis of oral lichen planus according to Western versus Chinese traditional medicine: Is the truth somewhere in-between?

Oral lichen planus (OLP) is considered a jeopardizing common chronic potentially malignant disease. Its etiology is yet undiscovered and pathogenesis has tangled elements; therefore, it receives symptomatic management rather than eradicative treatment. This is reflected in lower levels of quality of life and poorer prognosis. The disease is described by Western medicine techniques to be stimulated by an antigen, that is thought to be pathogenic bacteria. It was also discovered that changes in bacterial community of the gastrointestinal tract and liver reflect as changes in the oral microbial community, giving rise to overgrowth of pathogenic bacteria. On the other hand, Traditional Chinese medicine (TCM) has long described oral lichen planus as a consequence of spleen, liver and kidney deficiency with blood stasis. So, the authors question if the absolute truth about this mysterious disease is somewhere between the concepts of Western medicine and TCM. This correspondence aims to direct the attention to a more wholistic method of assessing and studying the disease following TCM footsteps. By doing so, OLP is expected to be effectively treated and its jeopardy would be a fairytale of the past. If future research corroborates the idea of this communication, a patient having oral lichen planus -who is nowadays asked to adapt with the disease and palliate its symptoms- will finally be cured of the disease completely.

Oral Lichen Planus: An Updated Review of Etiopathogenesis, Clinical Presentation, and Management.

Lichen planus (LP) is a chronic idiopathic immune-mediated inflammatory condition. LP is a heterogeneous disease with varied clinical presentations having different natural history, prognosis, sequelae, and outcomes. It can affect skin, hair, nails, and mucosae. Mucosal LP (including oral LP) tends to be persistent and resistant to treatment, compared to cutaneous LP. Oral LP (OLP) is broadly divided into two main categories: hyperkeratotic (usually asymptomatic) and erosive (commonly symptomatic). It can present with symptoms including odynophagia, dysphagia, dysgeusia, and sensitivity to hot spicy foods. Apart from the superficial epidermal changes, which vary with the type of clinical presentation, histopathologically oral LP shows a unifying similar and consistent feature of a lichenoid interface dermatitis. Recently, researchers have highlighted the critical role played by IL-17 in the pathogenesis of OLP. World Health Organization has categorized oral LP as one of the oral potentially malignant disorders (OPMD), albeit with a low risk of malignant transformation. Also, in the last couple of years there have been various reports on the usage of newer drugs like anti-IL17, anti-IL12/23, anti-IL 23, PDE4 inhibitors, and JAK inhibitors in the management of refractory OLP. The principal aim of treatment still remains to resolve the symptoms, prolong the symptoms free period, and reduce the risk of potential malignant transformation. We have described many new revelations made in recent times regarding the etiopathogenesis, associated conditions as well as management of OLP. Thus, the objective of this review is to present a comprehensive up-to-date knowledge including the recent advances made regarding OLP.

Patients with oral lichen planus display lower levels of salivary acidic glycoproteins than individuals without oral mucosal disease

ObjectivesSalivary proteins, acidic glycoproteins, and free calcium might take part in oral mucosal defence against inflammation in oral lichen planus (OLP). The study aimed to investigate whether the levels of sulfated and sialylated glycoproteins, total protein, and free calcium in saliva from patients with OLP differ from those of individuals without oral mucosal diseases.Material and MethodsPatients diagnosed with OLP (n = 25) and two control groups without any oral mucosal disease; age- and gender-matched controls (n = 25, 65.6 ± 2.9 years), and younger controls (n = 25, 41.8 ± 2.5 years) were included. Subjective dry mouth (xerostomia) was assessed by asking a single-item question. Chew-stimulated whole saliva was collected to measure sulfated and sialylated glycoproteins by the Alcian Blue method. The total protein was determined spectrophotometrically, and the free calcium measured using an electrode.ResultsThe output of salivary sulfated and sialylated glycoproteins in the OLP group (21.8 ± 2.4 µg/min) was lower than in the age- and gender-matched controls (43.0 ± 2.9 µg/min, p = 0.0002), whereas the total protein and calcium output did not differ between the three groups (p > 0.05). The prevalence of xerostomia was significantly higher in the OLP group compared to both control groups (p = 0.038).ConclusionsPatients with OLP showed a high prevalence of xerostomia and lower levels of salivary acidic type glycoproteins compared to the individuals without oral mucosa disease.Clinical relevanceIt is relevant to investigate the role of acidic glycoproteins in the pathogenesis of OLP.

Non-Coding RNAs as Potential Targets for Diagnosis and Treatment of Oral Lichen Planus: A Narrative Review.

Oral lichen planus (OLP) is a chronic inflammatory disease that is characterized by the infiltration of T cells into the oral mucosa, causing the apoptosis of basal keratinocytes. OLP is a multifactorial disease of unknown etiology and is not solely caused by the malfunction of a single key gene but rather by various intracellular and extracellular factors. Non-coding RNAs play a critical role in immunological homeostasis and inflammatory response and are found in all cell types and bodily fluids, and their expression is closely regulated to preserve normal physiologies. The dysregulation of non-coding RNAs may be highly implicated in the onset and progression of diverse inflammatory disorders, including OLP. This narrative review summarizes the role of non-coding RNAs in molecular and cellular changes in the oral epithelium during OLP pathogenesis.

Toll-like receptor 9-positive plasmacytoid dendritic cells promote Th17 immune responses in oral lichen planus stimulated by epithelium-derived cathepsin K

Oral lichen planus (OLP) is a chronic inflammatory disease associated with T cell infiltration. The crosstalk between oral epithelium and mucosal T cells was considered to be crucial in the pathogenesis of OLP. Here, we selectively extracted the normal epithelium (NE) and lesional epithelium (LE) of buccal mucosa specimens from three patients with OLP by laser capture microdissection due to identify the pathogenic factors. Cathepsin K (CTSK) was identified as one of common upregulated genes in the LE by DNA microarray. Immunohistochemically, CTSK was distinctly detected in and around the LE, while it was rarely seen in the NE. Recent studies showed that CTSK enhanced Toll-like receptor 9 (TLR9) signaling in antigen-presenting cells, leading to Th17 cell differentiation. TLR9 expression mainly co-localized with CD123+ plasmacytoid dendritic cells (pDCs). The number of RORγt-positive cells correlated with that of CTSK-positive cells in OLP tissues. CD123+ pDCs induced the production of Th17-related cytokines (IL-6, IL-23, and TGF-β) upon stimulation with TLR9 agonist CpG DNA. Moreover, single cell RNA-sequencing analysis revealed that TLR9-positive pDCs enhanced in genes associated with Th17 cell differentiation in comparison with TLR9-negative pDCs. CTSK could induce Th17-related production of CD123+ pDCs via TLR9 signaling to promote the pathogenesis of OLP.

Evaluation of the salivary level of glutathione reductase, catalase and free thiol in patients with oral lichen planus

ObjectiveOral lichen planus (OLP) is a usual chronic inflammatory disease of the oral mucosa with malignant capacity, whose pathogenesis is not yet well known. Free radicals and reactive oxygen species may have a vital role in the pathogenesis of oral lichen planus. This study aimed to assess Glutathione reductase, catalase, and free thiol levels in the saliva of OLP patients and compare it with healthy people.MethodsIn this cross-sectional study, 35 patients with OLP and 20 healthy people were involved. Five mL of whole, unstimulated saliva samples were collected in the morning, and the salivary levels of antioxidants were measured by ELISA technique. In this experiment, sex, age and OLP types were also evaluated.ResultsThere was a significant decrease in the patients’ salivary level of Glutathione reductase (0.2043 mU/ml in patients and 0.3901 mU/ml in the control group) and catalase (0.1525 mU/ml in patients and 0.2700 mU/ml in the control group) (p = 0.001). But there were no differences between the two groups regarding free-thiol levels (0.0586 mU/ml in patients and 0.0569 mU/ml in the control group) (p = 0.7). However, there was no correlation between age and gender with the antioxidants’ contents. There was a significant decrease in glutathione reductase and catalase in the erosive type than in the non-erosive type.ConclusionsIn this study, we found that the salivary levels of Glutathione reductase and Catalase were lower in OLP patients than in the healthy group, which means these antioxidants were affected by OLP and also associated with the type of it. So salivary Glutathione reductase and Catalase levels may be used as biomarkers for OLP monitoring and treatment.

Predictive values of salivary IL-6 and sFas-dependent apoptosis inhibitor in pathogenesis of oral lichen planus

Predictive values of salivary IL-6 and sFas-dependent apoptosis inhibitor in pathogenesis of oral lichen planus

The potential roles of Th17 cells in the pathogenesis of oral lichen planus.

Oral lichen planus (OLP) is a T cell-mediated chronic autoimmune disease, whose pathogenesis and etiology are not entirely understood. OLP is characterized by subepithelial lymphocyte infiltration and elevated intra-epithelial lymphocytes. The majority of lamina propria lymphocytes are CD4+ T cells. CD4+ helper T (Th) cells play a crucial role in activating CD8+ cytotoxic T cells (CTLs) through interactions and cytokine production. Th1 and Th2 cells are well-accepted to be associated with OLP pathogenesis. However, OLP treatment is challenging yet, the more information we have about the pathology of OLP, the easier it will be treated. With the discovery of Th17 cells in recent years and the demonstration of their role in autoimmune disease, many researchers started to investigate the role of Th17 in the pathogenesis of OLP. To make up this review, studies covering the role of TH17 in different types of lichen planus were selected from major databases. As we review in this article, Th17 cells and their signature cytokines play an important role in OLP pathogenesis. As well, utilizing some anti-IL-17 antibodies showed promising results in improving the disease; however, more studies are still needed to better understand and treat OLP.

Contact sensitisation in oral lichen planus: An Australian perspective.

The role of contact sensitisation in the pathogenesis of oral lichen planus (OLP) has not been clearly defined. We aimed to evaluate relevant contact sensitisers in OLP. A retrospective study was conducted on OLP patients who underwent patch testing from 1 January 2006 to 31 December 2020 at an Australian tertiary dermatology institution, compared to cheilitis patients patch tested over the same time period. Ninety-six OLP patients and 152 cheilitis patients were patch tested during the 15-year period. Seventy-one (73.9%) OLP patients and 100 (65.8%) cheilitis patients recorded one or more relevant reactions. Forty-three (44.8%), 22 (22.9%), 21 (21.9%) and 17 (17.7%) OLP patients had relevant reactions to mercury-related chemicals, amalgam, spearmint and carvone, respectively, compared to 6 (3.9%), 3 (2.0%), 4 (2.6%) and 0 (0%) cheilitis patients, respectively (p-value <0.001 each). Four (4.2%) OLP patients had relevant positive reactions to sodium metabisulfite, compared to none in the cheilitis group (p-value 0.021). While dental amalgam is used less frequently these days, we report that mercury (found in amalgam) and additionally spearmint and carvone are relevant sensitisers in OLP in Australia. Sodium metabisulfite may also be a relevant sensitiser in OLP, which has not previously been reported.

Immunological Aspects of EBV and Oral Mucosa Interactions in Oral Lichen Planus

Oral lichen planus (OLP) is considered a T cell-mediated chronic inflammatory process activated by an unknown antigen, making basal keratinocytes vulnerable to a cytotoxic cell mediated immune response. The aim of this review is to summarize information on the role and pathways of Epstein–Barr virus (EBV) and immune cells in inducing OLP as an autoimmune lesion. The pathogenesis of OLP is analyzed from immunological aspects of interactions between EBV and oral mucosa. The results of the available studies allow us to assume that EBV can act both as an exogenous and an endogenous antigen in the pathogenesis of OLP. We emphasized the role of antigen-presenting cells (APC), such as dendritic cells (Langerhans cells, LC), in detecting and capturing antigens and modulating the adaptive immune response. Although EBV shows tropism for B cells and epithelial cells, under certain conditions it can infect monocytes, LCs, NK, and T lymphocytes. It means that under some circumstances of the chronic inflammatory process, EBV particles can react as endogenous agents. During the development of the autoimmune process, a decisive role is played by the loss of immune tolerance. Factors like the activity of cytokines, chemokines, and autoantibodies secreted by EBV-positive plasma cells, autoantigens formed due to virus protein mimicry of human proteins, new self-peptides released from damaged tissues, self-reactive B and T cells, dysregulation of LC function, the anti-apoptotic effect of EBV early lytic antigens, and an imbalance between inflammatory and anti-inflammatory immune cells facilitate the development of an autoimmune process.

Lichen planus – A refractory autoimmune disorder

Lichen planus (LP) is a chronic inflammatory mucocutaneous disease of unknown aetiology with an estimated incidence of 0.5%–4.0% having a female preponderance at a ratio of 1.5:1. Oral lichen planus (OLP) is commoner than the cutaneous form and tends to be more persistent and more refractory to the treatment. The prevalence of oral lichen planus in Indian population is around 3% with more female predilection. Oral lesions occur in 50%–70% of the patients with lichen planus. LP is considered to be a T-cell-mediated autoimmune skin disease, in which CD8+ cytotoxic T lymphocytes are major mediators. TNF-α and IL-10, interferon-gamma (IFN-γ), IL-4, and IL-8, have been suggested to have an important role in the pathogenesis of OLP. The complications of Lichen Planus include post-inflammatory hyperpigmentation, scarring alopecia, dyspareunia, oesophageal stenosis &amp; possible malignant transformation. Mucocutaneous site biopsy can confirm the diagnosis when taken from the edge of a plaque. There is no cure for Lichen Planus, the management is often performed with the use of antihistamines, corticosteroids, retinoids, immunomodulators, phototherapy and immunosuppressives. Inconsistent results are shown by griseofulvin and chloroquine derivatives. (further prospective studies are needed).

Aberrant Activation of the STING-TBK1 Pathway in γδ T Cells Regulates Immune Responses in Oral Lichen Planus

Oral lichen planus (OLP) is a chronic T cell-mediated inflammatory disease. Interferon (IFN)-γ has been suggested to be vital for the OLP immune responses. A prominent innate-like lymphocyte subset, γδ T cells, span the innate-adaptive continuum and exert immune effector functions by producing a wide spectrum of cytokines, including IFN-γ. The involvement and mechanisms of γδ T cells in the pathogenesis of OLP remain obscure. The expression of γδ T cells in lesion tissues and in the peripheral blood of OLP patients was determined via flow cytometry and immunohistochemistry, respectively. Human leukocyte antigen-DR (HLA-DR), cluster of differentiation (CD) 69, Toll-like receptors (TLRs), natural killer group 2, member D (NKG2D) and IFN-γ were detected in γδ T cells of OLP patients using flow cytometry. Additionally, the involvement of stimulator of the interferon genes (STING)-TANK-binding kinase 1 (TBK1) pathway in γδ T cells was evaluated by multi-color immunofluorescence. Western blotting was employed to investigate the regulatory mechanisms of γδ T cells in OLP. γδ T cells were significantly upregulated in the lesion tissues, whereas their peripheral counterparts were downregulated in OLP patients. Meanwhile, increased frequencies of local CD69+ and NKG2D+ γδ T cells and peripheral HLA-DR+ and TLR4+ γδ T cells were detected in OLP. Furthermore, significant co-localization of STING and TBK1 was observed in the γδ T cells of OLP lesions. In addition, enhanced IFN-γ and interleukin (IL)-17A were positively associated with the activated STING-TBK1 pathway and γδ T cells in OLP. Taken together, the upregulated STING-TBK1 pathway in activated γδ T cells might participate in the regulation of immune responses in OLP.

Altered Expression of Vascular Cell Adhesion Molecule-1 in Oral Lichen Planus.

Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory mucocutaneous disease affected by the interaction between keratinocytes and T cells. Recent evidence indicates that vascular cell adhesion molecule-1 (VCAM1) plays a vital role in mediating immune and inflammatory responses. In this study, the expression of VCAM1 in OLP was detected by immunohistochemical staining and its correlations with clinical features were analyzed. The disease severity of OLP was assessed by the reticular, atrophic, and erosive scoring system. We found that VCAM1 was generally localized in the cytoplasm of epithelial cells, and in nucleus, cytoplasm, and extracellular matrix of subepithelial infiltrated cells in superficial layer of lamina propria. Moreover, VCAM1 levels in epithelium and lamina propria of OLP were significantly higher than that in controls, respectively. In addition, VCAM1 level in epithelium was increased compared with that of lamina propria. There were no significant differences for VCAM1 expression between nonerosive and erosive forms of OLP. The expression of VCAM1 in OLP was not associated with the severity of disease, gender, and age. Thus, we speculated that spatial expression differences of VCAM1 in local lesions of OLP may involve the pathogenesis of OLP.