Pathogenesis Of Oral Lichen Planus Research Articles

Alterations of oral microbiome and metabolic signatures and their interaction in oral lichen planus

ABSTRACT Background Oral lichen planus (OLP) is a chronic oral mucosal inflammatory disease with a risk of becoming malignant. Emerging evidence suggests that microbial imbalance plays an important role in the development of OLP. However, the association between the oral microbiota and the metabolic features in OLP is still unclear. Methods We conducted 16S rRNA sequencing and metabolomics profiling on 95 OLP patients and 105 healthy controls (HC).To study oral microbes and metabolic changes in OLP, we applied differential analysis, Spearman correlation analysis and four machine learning algoeithms Results The alpha and beta diversity both differed between OLP and HC. After adjustment for gender and age, we found an increase in the relative abundance of Pseudomonas, Aggregatibacter, Campylobacter, and Lautropia in OLP, while 18 genera decreased in OLP. A total of 153 saliva metabolites distinguishing OLP from HC were identified. Notably, correlations were found between Oribacterium, specific lipid and amino acid metabolites, and OLP’s clinical phenotype. Additionally, the combination of Pseudomonas, Rhodococcus and (±)10-HDoHE effectively distinguished OLP from HC. Conclusions Based on multi-omics data, this study provides comprehensive evidence of a novel interplay between oral microbiome and metabolome in OLP pathogenesis using the oral microbiota and metabolites of OLP patients.

Pathogenic relevance of antibodies against desmoglein3 inpatients with oral lichen planus.

Oral lichen planus (OLP) is a Tcell driven disorder that significantly impairs patients' quality of life. Previous reports suggest that both cellular and humoral activities against desmoglein (dsg) 1 and 3 may be involved in OLP pathogenesis. Here, we aim to analyze the frequency of occurrence and pathological significance of anti-dsg antibodies in a large cohort of OLP patients. OLP patients were screened for anti-dsg antibodies by enzyme-linked immunosorbent assay in three tertiary referral centers. OLP sera with anti-dsg antibodies were further analyzed by Western blot and dispase-based keratinocyte dissociation assay (DDA) to identify the targeted dsg ectodomains and to assess their pathogenicity. Of 151-screened individuals with OLP, only four patients (2.6%) with erosive OLP showed serum IgG against dsg1/3. Western blot analysis with recombinant dsg3 ectodomains revealed preferential recognition of the extracellular domain 5. By DDA with spontaneously immortalized human keratinocytes, none of the sera from these four patients induced acantholysis. Activation of humoral immunity occurs prevalently in patients with erosive OLP, probably due to epitope spreading. OLP serum antibodies are unable to induce loss of intercellular adhesion in vitro, strongly suggesting that they are not disease causing but rather an epiphenomenon.

A Tissue-Engineered Model of T-Cell–Mediated Oral Mucosal Inflammatory Disease

T-cell-mediated oral mucocutaneous inflammatory conditions including oral lichen planus (OLP) are common but development of new treatments aimed at relieving symptoms and controlling OLP progression are hampered by the lack of experimental models. Here, we developed a tissue-engineered oral mucosal equivalent (OME) containing polarised T-cells to replicate OLP pathogenesis. Peripheral blood CD4+ and CD8+ T-cells were isolated, activated and polarised into Th1 and cytotoxic T-cells (Tc). OME were constructed by culturing oral keratinocytes on an oral fibroblast-populated hydrogel to produce a stratified squamous epithelium. OME stimulated with IFN-γ and TNF-α or medium from Th1 cells caused increased secretion of inflammatory cytokines/chemokines. A model of T-cell-mediated inflammatory disease was developed by combining OME on top of a Th1/Tc-containing hydrogel, followed by epithelial stimulation with IFN-γ/TNF-α. T-cell recruitment towards the epithelium was associated with increased secretion of T-cell chemoattractants CCL5, CXCL9 and CXCL10. Histological assessment showed tissue damage associated with cleaved-caspase-3 and altered laminin-5 expression. Treatment with inhibitors directed against JAK, KCa3.1 channels or clobetasol in solution and/or via a mucoadhesive patch prevented cytokine/chemokine release and tissue damage. This disease model has potential to probe for mechanisms of pathogenesis or as a test platform for novel therapeutics or treatment modalities.

Oral Lichen Planus: A Narrative Review Navigating Etiologies, Clinical Manifestations, Diagnostics, and Therapeutic Approaches.

Background/Objectives: Oral Lichen Planus (OLP) is a common immune-mediated inflammatory disorder affecting the oral mucosa, impacting 0.5% to 2% of the global population, primarily middle-aged women. Immunological dysregulation is a key factor in OLP's pathogenesis, involving CD4+ T helper and CD8+ T cytotoxic cells. The World Health Organization (WHO) classifies OLP as a potentially malignant disorder, with a risk of oral squamous cell carcinoma (OSCC) developing in up to 2% of lesions. This narrative review aims to provide a comprehensive overview of the etiopathogenesis, clinical manifestations, diagnostic criteria, and therapeutic strategies for OLP, informing clinical practice and guiding future research. Methods: A review of the literature from the PubMed and Google Scholar databases was conducted up to December 2023, focusing on studies addressing the etiopathogenesis, diagnosis, clinical manifestations, and treatment of OLP. Results: OLP's pathogenesis is driven by immune dysregulation, with CD4+ and CD8+ cells playing crucial roles. Clinically, OLP presents as reticular, erosive, bullous, and plaque-like lesions. Diagnosis relies on clinical examination, histopathology, and direct immunofluorescence. Recent advancements in diagnostic markers and imaging techniques have improved detection and monitoring. Treatment primarily involves corticosteroids, but novel therapies such as curcumin, retinoids, and laser therapy are increasingly used for their effectiveness and reduced side effects. These treatments show promise in symptom reduction and recurrence prevention, although long-term data are needed. Conclusions: Regular screenings and biopsies are essential due to OLP's likelihood of malignant transformation. This study urges further investigation into long-term results, improved diagnostic techniques, and evidence-based treatment regimens.

The relationship of microbial biodiversity and clinical forms of oral lichen planus: analysis based on 16S rRNA sequencing

BACKGROUND: The composition and changes of microbiota have a significant impact on overall health and the development of various diseases. Of particular relevance is the problem of changes in the oral microbiota in patients with lichen planus of the oral mucosa. Studying the relationship between the composition of the oral microbiota and the pathogenesis of oral lichen planus will improve the understanding of the mechanisms of this disease. Thus, this topic is of considerable interest to a wide range of specialists in the field of medicine and biology. AIM: Detailed analysis of oral cavity microbiota and establishment of potential pathogenetic microbial associations with oral lichen planus. MATERIALS AND METHODS: The study included samples from patients diagnosed with various forms of oral red squamous lichen planus (lichen planus erosive-ulcerative) and a control group. The investigation was based on analyzing microbial diversity metrics (alpha and beta diversity), relative abundance of bacterial taxa, and identification of unique bacterial taxa in the oral red squamous lichen planus patients. This analysis utilized the 16S rRNA sequencing method. RESULTS: The analysis revealed a rich bacterial composition in patients with oral lichen planus, which was significantly different from that in the control group. Differences were also observed between the subgroups, especially between the typical and erosive-ulcerative forms of the disease. Notably, beta diversity did not show significant differences between the groups, indicating a similar overall microbiota composition despite fluctuations in the relative abundance of species. Nevertheless, the typical clinical form of the disease demonstrated more significant differences in the microbiota structure compared to the hyperkeratotic and erosive-ulcerative forms. Furthermore, analysis of the study groups revealed the presence of 50% shared microbial species, while the other half was represented by unique species associated with oral lichen planus. Regarding the subgroups, it was found that unique microorganisms correlated with the typical and erosive-ulcerative forms, respectively, providing a deeper understanding of the specific microbiological profile in the context of this disease. CONCLUSION: The study confirmed the hypothesis of an association between the microbiota composition and oral lichen planus, which may be of importance for the development of novel therapeutic approaches.

Potential role of salivary lactic acid bacteria in pathogenesis of oral lichen planus

BackgroundEmerging evidence emphasized the role of oral microbiome in oral lichen planus (OLP). To date, no dominant pathogenic bacteria have been identified consistently. It is noteworthy that a decreased abundance of Streptococcus, a member of lactic acid bacteria (LAB) in OLP patients has been commonly reported, indicating its possible effect on OLP. This study aims to investigate the composition of LAB genera in OLP patients by high-throughput sequencing, and to explore the possible relationship between them.MethodsWe collected saliva samples from patients with OLP (n = 21) and healthy controls (n = 22) and performed 16 S rRNA gene high-throughput sequencing. In addition, the abundance of LAB genera was comprehensively analyzed and compared between OLP and HC group. To verify the expression of Lactococcus lactis, real time PCR was conducted in buccal mucosa swab from another 14 patients with OLP and 10 HC. Furthermore, the correlation was conducted between clinical severity of OLP and LAB.ResultsOLP and HC groups showed similar community richness and diversity. The members of LAB, Lactococcus and Lactococcus lactis significantly decreased in saliva of OLP cases and negatively associated with OLP severity. In addition, Lactococcus and Lactococcus lactis showed negative relationship with Fusobacterium and Aggregatibacter, which were considered as potential pathogens of OLP. Similarly, compared with healthy controls, the amount of Lactococcus lactis in mucosa lesion of OLP patients was significantly decreased.ConclusionsA lower amount of Lactococcus at genus level, Lactococcus lactis at species level was observed in OLP cases and associated with disease severity. Further studies to verify the relationship between LAB and OLP, as well as to explore the precise mechanism is needed.

A Study on the Correlation between the Expression of a Cysteine Protease, Cathepsin L, and its Inhibitor, Cystatin A, in Oral Lichen Planus

Background Cathepsin L (Cat-L), a cysteine protease, and cystatin A (Cys-A), a cysteine protease inhibitor, are known to be involved in Oral Lichen Planus (OLP). The imbalance in expression between these two proteins may favor OLP pathogenesis. Objective This study aimed to evaluate the correlation between the expression of Cat-L and Cys-A in OLP. Methods Thirty specimens of OLP and 30 specimens of normal tissue were used for immunohistochemistry. The pattern of cell staining, number of positive cells, and cell staining intensity were recorded. An Immunoreactive Score (IRS) was also assigned. Results Cat-L and Cys-A were found in all OLP specimens. In the control group, Cat-L and Cys-A were demonstrated in 83.33% and 96.67% of cases, respectively. Cat-L was primarily seen in the stratum basale in the OLP and control groups. In contrast, Cys-A expression was seen in the whole epithelium in both groups, and the intensity was lowest in the stratum basale. The percentage of positive cells, score of positive cells, staining intensity, and IRS of Cat-L and Cys-A were significantly higher in OLP than in control specimens (p < 0.05). Interestingly, a positive correlation between Cat-L and Cys-A was found in the control group but not in the OLP group. Conclusion The expressions of Cat-L and Cys-A were significantly higher in OLP tissues compared to normal tissues. The alterations in expression of the Cat-L cysteine protease and its Cys-A inhibitor in OLP may indicate that these two proteins play a role in the pathogenesis of OLP.

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.

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. This study was conducted to evaluate the role of oral microorganisms in the pathogenesis of OLP. 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. 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. 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.

COVID-19 and its possible association with oral lichen planus: An institutional experience

Introduction: Lichen planus is a chronic mucocutaneous disease that may affect the skin or any other mucosal surface. Although the etiology is largely unknown, role of stress in initiation or aggravation of the disease is a well-known fact. Apart from respiratory distress, COVID-19 has also been found to be associated with triggering autoimmune reactions such as oral lichen planus (OLP). Apart from its direct ill effect on health, the confusing nature, and the unknown course of COVID-19, the psychological stress of the lockdown and quarantine tremendously increased the stress levels. All this could be a trigger for the onset or exacerbation of existing OLP lesions. Objective: The primary outcome is to understand the likely association between OLP and COVID-19. The secondary outcome is to understand the role of COVID-19 in the pathogenesis of OLP if it is present. Materials and Methods: It was a unicentric cross-sectional study conducted on 57 patients suffering from OLP who had reported to the dental outpatient department of our tertiary health care center from September 2021 to April 2022. The clinical sign and symptoms associated with the OLP was recorded. A detailed history of COVID-19 exposure, vaccination status, and history of hospitalization were recorded. Results: The mean age of study participants was found to be 36.8 years the male:female ratio was found to be 1:2. Out of 57 patients, 45 patients had given a positive history of COVID-19 exposure. Conclusion: Apart from the immune dysregulation, the tremendous increase in stress levels due to COVID-19 has impacted everyone’s life very badly. The sudden increase in cases of OLP in post-COVID patients may be attributable to a combination of factors such as low Vitamin D levels COVID-19 and other comorbidities.

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.