γδ T cells in oral diseases.

OBJECTIVE: γδ T cells are a distinct subset of unconventional T cells, which link innate and adaptive immunity by secreting cytokines and interacting with other immune cells, thereby modulating immune responses. As the first line of host defense, γδ T cells are essential for mucosal homeostasis and immune surveillance. When abnormally activated or impaired, γδ T cells can contribute to pathogenic processes. Accumulating evidence has revealed substantial impacts of γδ T cells on the pathogenesis of cancers, infections, and immune-inflammatory diseases. γδ T cells exhibit dual roles in cancers, promoting or inhibiting tumor growth, depending on their phenotypes and the clinical stage of cancers. During infections, γδ T cells exert high cytotoxic activity in infectious diseases, which is essential for combating bacterial and viral infections by recognizing foreign antigens and activating other immune cells. γδ T cells are also implicated in the onset and progression of immune-inflammatory diseases. However, the specific involvement and underlying mechanisms of γδ T cells in oral diseases have not been systematically discussed. METHODS: We conducted a systematic literature review using the PubMed/MEDLINE databases to identify and analyze relevant literature on the roles of γδ T cells in oral diseases. RESULTS: The literature review revealed that γδ T cells play a pivotal role in maintaining oral mucosal homeostasis and are involved in the pathogenesis of oral cancers, periodontal diseases, graft-versus-host disease (GVHD), oral lichen planus (OLP), and oral candidiasis. γδ T cells mainly influence various pathophysiological processes, such as anti-tumor activity, eradication of infection, and immune response regulation. CONCLUSION: This review focuses on the involvement of γδ T cells in oral diseases, with a particular emphasis on the main functions and underlying mechanisms by which γδ T cells influence the pathogenesis and progression of these conditions. This review underscores the potential of γδ T cells as therapeutic targets in managing oral health issues.

T cell-derived exosomes containing cytokines induced keratinocytes apoptosis in oral lichen planus.

OBJECTIVE: Oral lichen planus (OLP) is a T cell-mediated inflammatory disease with uncertain etiology. Exosomes are cell-derived vesicles containing biological cargo, being associated with the development of multiple inflammatory diseases. The present study aims to investigate the role of T cell-derived exosomes in the pathogenesis of OLP. METHODS: Exosomal marker CD63 was detected in OLP lesions by immunohistochemistry. Twenty-three cytokines in T cell-derived exosomes were assessed using luminex xMAP-based assay. After co-incubating with exosomes, the apoptosis of keratinocytes and the proliferation of Jurkat cells were assessed via flow cytometry and cell counting kit-8 assay, respectively. RESULTS: CD63 was highly expressed in the lymphocyte infiltrated areas of OLP lesions. OLP T cell-derived exosomes contained upregulated interleukin-7, -10, -12, -17 and downregulated interleukin-1ß, -5, and interferon-γ. Both exosomes from OLP patients and controls induced the apoptosis of keratinocytes and altered their morphology. Moreover, healthy control-derived exosomes markedly inhibited the proliferation of Jurkat cells, whereas OLP-derived exosomes exhibited no inhibitory effect. CONCLUSIONS: OLP T cell-derived exosomes have an aberrant cytokine profile and could trigger the apoptosis of keratinocytes in vitro, which may be involved in the pathogenesis of OLP.

T cell-derived exosomes induced macrophage inflammatory protein-1α/ß drive the trafficking of CD8+ T cells in oral lichen planus.

Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory disease with uncertain aetiology. Exosomes are nanosized particles with biological capacities. Here, we aimed to study the effects of T cell-derived exosomes (T-exos) on the pathogenesis of OLP and its mechanism. T-exos were incubated with Jurkat cells for 48 hours, and 26 cytokines in the supernatant were measured by luminex assay. The expression of macrophage inflammatory protein (MIP)-1α/ß was detected using immunohistochemistry and ELISA; that of CCR1/3/5 on peripheral T cells was determined by flow cytometry. Transwell assay was performed to investigate the chemotactic effect of MIP-1α/ß, and cells in the lower chambers were examinated by flow cytometry. As a result, OLP T-exos elevated the production of MIP-1α/ß, which were highly expressed in OLP tissues and plasma. CCR1/5 were markedly expressed on OLP peripheral T cells, and the majority of CCR1/5+ T cells were CD8+ T cells. Besides, MIP-1α/ß promoted the migration of OLP mononuclear cells, while inhibiting CCR1/5 significantly decreased the trafficking of mononuclear cells, especially that of CD8+ T cells. Conclusively, OLP T-exos-induced MIP-1α/ß may drive the trafficking of CD8+ T cells after binding with CCR1/5 in OLP, contributing to the development of OLP.

Omega-3 polyunsaturated fatty acids: a promising approach for the management of oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a T-cell-mediated inflammatory disease with a risk of malignant transformation. Although the etiology of OLP is still uncertain, growing evidence suggests that oral microbiota, antigen-specific, and non-specific mechanisms are involved in the pathogenesis of OLP. Antigen-specific mechanisms include antigen presentation, T-cell activation, nuclear factor-kappa B signaling pathway, and cytokine secretion, while non-specific mechanisms consist of matrix metalloproteinases (MMP)-9 upregulation, psychological pressure, oxidative damage, aberrant expression of microRNAs (miRNAs), and autophagy. Till now, there is no cure for OLP, and the main purpose of OLP therapy is symptomatic control. FINDING: Seafood and its derivative omega-3 polyunsaturated fatty acids (n-3 PUFAs) can suppress antigen presentation, T-cell activation, and nuclear factor-kappa B signaling pathway, modulate the overexpressed inflammatory cytokines, inhibit the expression of MMP-9, as well as regulate the expression of miRNAs and autophagy. And they are possible agents for ameliorating psychological disorder and oxidative damage. Moreover, n-3 PUFAs supplementation has a beneficial effect on preventing tumorigenesis. CONCLUSION: n-3 PUFAs consumption may provide a non-toxic, inexpensive administration for OLP.

Familial oral lichen planus in a 3-year-old boy: a case report with eight years of follow-up.

BACKGROUND: Oral lichen planus (OLP) is a chronic mucocutaneous disease characterized by adult predominance and a prolonged course. However, it is rare in the pediatric population with familial aggregation. CASE PRESENTATION: A 3-year-old boy presented with pain and irritation on the oral mucosa while contacting spicy food for 2 months. Oral examination showed widespread whitish reticular and papular lesions on the lips, the dorsum of the tongue, and bilateral buccal mucosa, with diffuse erosions covered with pseudomembrane on the buccal mucosa. The boy's parents were examined to exhibit white reticular and plaque-like lesions on their oral mucosa. The three patients were clinically diagnosed as affected by OLP and histopathologically confirmed. The boy underwent topical treatment with recombinant bovine basic fibroblast growth factor (rb-bFGF) gel, and oral lesions gradually resolved and healed. Neither of his parents received treatment. During the subsequent follow-ups, none of three patients underwent any medical treatment. Fortunately, their lesions had almost faded over 8 years. CONCLUSIONS: Our case emphasizes that pediatric OLP should be recorded with family history. Besides, long-term periodic follow-up is recommended in pediatric patients with OLP for monitoring any changes in lesions.

Heterogeneity of Outcome Measures Used in Randomized Controlled Trials for the Treatment of Oral Lichen Planus: A Methodological Study.

OBJECTIVE: Oral lichen planus (OLP) is a chronic inflammatory immune disease, recognized as an oral potentially malignant disorder by the World Health Organization. There is considerable controversy over the standardized treatment of OLP, with great diversities in the outcome measures in clinical trials. This methodological study aimed to estimate the degree of consensus on outcome measures in randomized controlled trials (RCTs) for OLP treatment. METHODS: PubMed, Embase, and Cochrane databases were searched to identify RCTs published from 2004 to 2018 about OLP treatment. All the outcome measures and measurement methods mentioned in the trials were extracted and analyzed. RESULTS: After identification of 1087 articles, 88 RCTs were included. A total of 193 single-outcome measures and 119 composite outcome measures were classified into 11 different domains, the chief of which consisted of clinical symptom (78 trials; 88.6%) and clinical score (58 trials; 65.9%). Visual analog scale (65 trials; 73.9%) and Thongprasom scoring system (38 trials; 43.2%) were the predominant measurement methods. Oral health-related quality of life (except for clinical symptoms) accounted for 4.8% of all the outcome measures. CONCLUSIONS: There was high heterogeneity in outcome measures of RCTs for OLP treatment, making it difficult to make valid comparisons between different clinical trials. A core outcome set should be developed and adopted in future trials for OLP treatment.

Artemisinin and its derivatives: a potential therapeutic approach for oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a common T-cell-mediated oral mucosal disease, whose pathogenesis mainly includes antigen-specific and non-specific mechanisms. As a refractory chronic inflammatory disease, there is still no curable management for OLP till now. FINDINGS: Artemisinins are a family of compounds that are widely used as frontline treatment for malaria worldwide. In addition to its well-established antimalarial properties, emerging evidence hints that artemisinin family drugs also possess preferential immunoregulatory and anti-inflammation properties, such as modifying T lymphocytes' activation and cytokines release, modulating Th1/Th2 balance, activating regulatory T cells (Tregs), modulating inflammatory signaling pathways, as well as acting on non-specific mechanisms of OLP. However, there is still no report focused on the influence of artemisinins on OLP. CONCLUSION: This review outlined the data-based immunomodulatory effects of artemisinins on different immune cells in conjunction with their therapeutic prospective with regard to the pathogenesis of OLP, suggesting that artemisinin and its derivatives might be possible candidates for treatment of OLP.

TLR4-induced B7-H1 on keratinocytes negatively regulates CD4+ T cells and CD8+ T cells responses in oral lichen planus.

Oral lichen planus (OLP) is a T-cell-mediated autoimmune mucocutaneous disease affected by the interactions among the keratinocytes, CD4+ T cells and CD8+ T cells. B7-H1 induced by Toll-like receptors (TLRs) can suppress T-cell immune reaction, thereby resulting in immune tolerance. However, the role of TLR-mediated B7-H1 on keratinocytes in the immune response of OLP is still unknown. The present study showed that TLR4 could induce time-coursed B7-H1 expression on oral keratinocytes, and blocking NF-κB or PI3K/mTOR pathway downregulated B7-H1 transcriptional expression. Moreover, TLR4-stimulated oral keratinocytes inhibited the proliferation of OLP CD4+ T cells and OLP CD8+ T cells, and simultaneously prompted their apoptosis. Blockade of keratinocyte-associated B7-H1 restored the declined proliferation of OLP CD4+ T cells and OLP CD8+ T cells, and prevented their increased apoptosis. Therefore, TLR4-upregulated B7-H1 on keratinocytes could decelerate immune responses of CD4+ T cells and CD8+ T cells in OLP.

Increased circulating CXCR5+ CD4+ T follicular helper-like cells in oral lichen planus.

BACKGROUND: CD4+ T-helper cell is crucial for the inflammatory autoimmune condition of oral lichen planus (OLP). Recently, the pathogenetic functions of T follicular helper (Tfh) cells, a subtype of CD4+ T-helper cells, have been revealed in autoimmune diseases for their pivotal regulation on humoral immunity. To explore the potential pathophysiological role of Tfh cells in OLP, the expression of circulating Tfh-like cells and its correlations with IL-21 and B cells were investigated. METHODS: The frequencies of CXCR5+ CD4+ Tfh-like cells and CD19+ B cells were analyzed in peripheral blood of patients with OLP and controls by flow cytometry, respectively. Besides, the serum IL-21 concentration was measured using ELISA technology. Furthermore, the correlations of CXCR5+ CD4+ Tfh-like cells with CD19+ B cells and serum IL-21 expression levels were evaluated. RESULTS: This study showed significant increased circulating Tfh-like cells (P < 0.05) and B cells (P < 0.0001), as well as decreased serum IL-21 expression (P < 0.001) in OLP. Besides, the frequency of Tfh-like cells exhibited negative correlation with B cells in OLP (r = -0.435, P < 0.05). In particular, the proportion of CXCR5+ CD4+ Tfh-like cells in peripheral blood mononuclear cells of erosive OLP was higher than non-erosive OLP and controls (P = 0.012 and 0.021, respectively). CONCLUSIONS: Increased circulating Tfh-like cells may be involved in the pathogenesis of OLP through abnormal modulation on B-cell proliferation and IL-21 production, and associated with different clinical forms of OLP.

Icaritin Reduces Oral Squamous Cell Carcinoma Progression via the Inhibition of STAT3 Signaling.

Icaritin, a traditional Chinese medicine, possesses antitumor activity. The current study aimed to investigate icaritin effect and potential mechanism on oral squamous cell carcinoma (OSCC) development. OSCC cells proliferation, apoptosis, and autophagy were analyzed after incubation with icaritin at different concentrations and incubation times. The expressions of proteins related to proliferation, apoptosis, and autophagy, as well as signal transducer and activator of transcription 3 (STAT3) signal network, were also evaluated by western blot. Furthermore, STAT3 was knocked down by siRNA transfection to determine STAT3 role in OSCC cell proliferation and apoptosis. An oral specific carcinogenesis mouse model was used to explore icaritin effect on OSCC in vivo. Icaritin significantly inhibited OSCC proliferation in vitro and reduced the expression of both the cell-cycle progression proteins cyclin A2 and cyclin D1. Besides, icaritin increased cleaved caspase 3 and cleaved poly-(ADP-ribose) polymerase expression leading to apoptosis, and it activated autophagy. Icaritin significantly inhibited the expression of phospho-STAT3 (p-STAT3) in a dose- and time-dependent manner. In the in vivo experiment, the number of malignant tumors in the icaritin-treated group was significantly lower than the control. Overall, icaritin suppressed proliferation, promoted apoptosis and autophagy, and inhibited STAT3 signaling in OSCC in vitro and in vivo. In conclusion, icaritin might be a potential therapeutic agent against OSCC development.

Altered Autophagy-Associated Genes Expression in T Cells of Oral Lichen Planus Correlated with Clinical Features.

Oral lichen planus (OLP) is a T cell-mediated inflammatory autoimmune disease. Autophagy has emerged as a fundamental trafficking event in mediating T cell response, which plays crucial roles in innate and adaptive immunity. The present study mainly investigated the mRNA expression of autophagy-associated genes in peripheral blood T cells of OLP patients and evaluated correlations between their expression and the clinical features of OLP. Five differentially expressed autophagy-associated genes were identified by autophagy array. Quantitative real-time RT-PCR results confirmed that IGF1 expression in the peripheral blood T cells of OLP patients was significantly higher than that in controls, especially in female and middle-aged (30-50 years old) OLP patients. In addition, ATG9B mRNA levels were significantly lower in nonerosive OLP patients. However, no significant differences were found in the expression of HGS, ESR1, and SNCA between OLP patients and controls. Taken together, dysregulation of T cell autophagy may be involved in immune response of OLP and may be correlated with clinical patterns.

Autophagy-related 9 homolog B regulates T-cell-mediated immune responses in oral lichen planus.

OBJECTIVES: This study aimed to explore the impacts of autophagy-related 9 homolog B (ATG9B)-mediated autophagy on T-cell immune responses in oral lichen planus. DESIGN: ATG9B expression was detected in lesions and local T cells by immunohistochemical analysis and immunofluorescence assay. The effects of ATG9B-mediated autophagy on T-cell immune responses were explored after ATG9B-overexpression or ATG9B-knockdown lentivirus transfection. A coculture system of activated T cells and lipopolysaccharide-induced keratinocytes was used to simulate the main cell crosstalk in oral lichen planus. RESULTS: The expression of ATG9B upregulated in lesions and local T cells of oral lichen planus, especially in non-erosive oral lichen planus, suggesting that ATG9B may be a diagnostic factor for oral lichen planus. Notably, ATG9B-knockdown T cells of oral lichen planus demonstrated autophagy suppression, enhanced proliferation, and attenuated apoptosis, whereas overexpression of ATG9B showed opposite effects on T cells. In the coculture system of T cells and keratinocytes, ATG9B-knockdown T cells of oral lichen planus, but not ATG9B-overexpression T cells, promoted the proliferation and apoptosis of their cocultured keratinocytes. Additionally, exogenous insulin-like growth factor 1 (IGF1) significantly reversed the apoptosis rates of keratinocytes cocultured with T cells expressing abnormal ATG9B. Furthermore, ATG9B-overexpression T cells showed decreased secretion of interferon-γ and tumor necrosis factor-α in the coculture system. CONCLUSIONS: This study revealed the regulatory roles of ATG9B-mediated T-cell autophagy on T-cell immune responses and crosstalk between T cells and keratinocytes in of oral lichen planus.

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.

Developmental synergism in the management of oral potentially malignant disorders.

Oral potentially malignant disorders (OPMDs) are associated with an increased risk of occurrence of cancers of the oral cavity or lips. The unifying theme of OPMDs is their potential risk for cancer development. Therefore, the primary objective of the management should be to prevent carcinogenesis. Beyond diagnosis, current strategies for the management of OPMDs predominantly include non-surgical and surgical interventions and a "watch-and-see" approach, such as disease monitoring or surveillance, and preventive strategies. Though no optimal clinical treatment has gained universal approval for reducing or preventing malignant development of OPMDs. Therefore, an urgent need exits for improved treatment properties and effective predictive markers for OPMDs treatment. This review aims to outline recent synergism regarding to the management of OPMDs. Developing new technologies and improved application parameters to promote the treatment efficacy and a novel management prescription approach to OPMDs are proposed.

Melatonin: a potential therapeutic approach for the management of primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is an autoimmune disease that primarily affects the exocrine glands and is mainly characterized by sicca symptoms of the eyes and mouth. Approximately 30-50% of pSS patients develop systemic multi-organ disorders including malignant lymphoma. The etiology of pSS is not well understood; growing evidence suggests that uncontrolled immune/inflammatory responses, excessive oxidative stress, defected apoptosis, dysregulated autophagy, exosomes, and exogenous virus infections may participate in the pathogenesis of pSS. There is no ideal therapeutic method for pSS; the management of pSS is mainly palliative, which aims to alleviate sicca symptoms. Melatonin, as the main secretory product of the pineal gland, has been evidenced to show various physiological functions, including effects of immunoregulation, capability of antioxidation, moderation of autophagy, suppressive activities of apoptosis, regulative capacity of exosomes, properties of anti-infection, and improvement of sleep. The beneficial effects of melatonin have been already validated in some autoimmune diseases such as multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD). However, our previous research firstly revealed that melatonin might inhibit pathogenic responses of peripheral Th17 and double-negative (DN) T cells in pSS. More importantly, melatonin administration alleviated the development of pSS in animal models with reduced infiltrating lymphocytes, improved functional activity of salivary gland, and decreased production of inflammatory factors as well as autoantibodies. Owing to the important biological properties reported in melatonin are characteristics closely related to the treatment of pSS; the potential role and underlying mechanisms of melatonin in the administration of pSS are certainly worth further investigations. Consequently, the aim of this review is to give a deep insight to the therapeutic potency of melatonin for pSS.

Multiple noninvasive auxiliary tests-assisted photodynamic therapy in actinic cheilitis: A case report.

Actinic cheilitis (AC) is recognized as the most common precursor lesion of squamous cell carcinoma (SCC) of the lip, with a higher risk of invasiveness and metastasis. Early accurate diagnosis and appropriate therapy are essential to prevent carcinogenesis and progression of AC. Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT), a non-surgical and minimally invasive modality, has been proposed as an effective treatment for oral potentially malignant diseases (OPMDs) and oral cancers. Herein, we report a 64-year-old female patient with AC on the lower lip who received 3 sessions of ALA-PDT with an interval of 1 week. Multiple noninvasive auxiliary tests including autofluorescence imaging, toluidine blue staining, and aneuploidy with DNA image cytometry (DNA-ICM) using brushing from screening through diagnosis, treatment, and follow-up. The patient successfully showed a complete response with no adverse effects and no evidence of recurrence at the 20-month follow-up. Noninvasive auxiliary tests assisted PDT is attractive and well-tolerated and may have synergistic effects against AC.

Different expression profiles of circulating miR-31 and miR-181a in CD4+ T cells and plasma of patients with oral lichen planus.

Oral lichen planus (OLP) is a T cell-mediated inflammatory-immune disease in which CD4+ T cells may be significantly involved in the dysregulated immune response. MicroRNAs (miRNAs) critically control gene expression post-transcriptionally and regulate the immune response and inflammation. Here, we explored the expression profiles of circulating miRs (miR-19b, miR-31, and miR-181a), which can modulate CD4+ T cell activation, differentiation, and immune function. Quantitative real-time PCR showed that miR-31 and miR-181a dramatically decreased in peripheral CD4+ T cells, whereas they markedly increased in the plasma of OLP patients, especially in the erosive form. However, no significant differences were observed in the expression of miR-19b in CD4+ T cells and plasma between OLP patients and healthy controls or between different forms of OLP. Moreover, miR-31 expression positively correlated with the miR-181a expression in the CD4+ T cells and plasma of OLP patients. Furthermore, receiver operating characteristic (ROC) curve analyses indicated that miR-31 and miR-181a, rather than miR-19b, in CD4+ T cells and plasma could discriminate OLP, especially erosive OLP, from healthy controls. In conclusion, there were different expression profiles of circulating miR-31 and miR-181a in CD4+ T cells and plasma of patients with OLP, which could synergistically serve as potential biomarkers for OLP.

Continuous artificial intelligence-assisted DNA aneuploidy cytology for surveilling dysplastic oral leukoplakia treated by photodynamic therapy.

Oral leukoplakia (OLK) is one of the most common potentially malignant disorders. High-risk lesions require early intervention before developing into oral cancer. Photodynamic therapy (PDT) is a noninvasive technique for premalignant lesions. Scalpel biopsy remains a reliable method for monitoring the prognosis of OLK, but it is an invasive procedure with poor reproducibility to suspicious lesions. DNA aneuploidy cytology by oral cytobrush has been proposed as a promising objective and noninvasive tool in screening and diagnosing premalignant and malignant lesions. Here, we discussed the significance of artificial intelligence (AI)-assisted DNA aneuploidy cytology by image cytometry (DNA-ICM) for surveilling non-homogeneous OLK with moderate-to-severe dysplasia that was treated by 5-aminolevulinic acid-mediated PDT (ALA-PDT). The present study provides a scheme of the sequential management and surveillance strategy for OLK.

Interferon-γ activated T-cell IRGM-autophagy axis in oral lichen planus.

Oral lichen planus (OLP) is an inflammatory immune disease featured by dense T-cell infiltrate and basal keratinocytes degeneration. Immunity related GTPase M (IRGM) is vital for the induction of autophagy. Our previous studies have demonstrated aberrant autophagy in OLP, however, the involvement of IRGM-autophagy axis in OLP has not yet been revealed. The expression of IRGM and autophagy activity were evaluated in oral mucosal tissues and peripheral T cells of OLP patients and healthy controls, respectively. We found significant upregulation of IRGM and LC3B in lesions of patients with OLP as compared with healthy donors. IRGM, LC3B and NOD2 levels were also elevated in the peripheral T cells of OLP. Then, knockdown of IRGM after electrotransfection with siRNA resulted in attenuated autophagy, growth inhibition, and apoptosis of T cells. In addition, preincubation with IFN-γ promoted the expression of IRGM mRNA and induced autophagy in T cells. Furthermore, IFN-γ decreased the proliferation and apoptosis of T cells, whereas facilitated the viability of keratinocytes in a co-culture system of activated T cells and keratinocytes. Taken together, activated IRGM-autophagy axis under IFN-γ regulation in T cells might participate in the immunoregulatory mechanism of OLP.

Targeting CD47 Inhibits Tumor Development and Increases Phagocytosis in Oral Squamous Cell Carcinoma.

BACKGROUND: Our previous work demonstrated upregulated CD47 in Oral Squamous Cell Carcinoma (OSCC). OBJECTIVE: In the present study, we aimed to investigate the effects of CD47 on tumor cell development and phagocytosis in OSCC and elucidate the underlying mechanisms. METHODS: The proliferation, apoptosis, migration, and invasion of oral cancer cells were analyzed after knocking down the expression of CD47. The effects of CD47 on tumor development were also evaluated using a murine model of OSCC. The involvement of CD47 in the phagocytosis of oral cancer cells was identified. RESULTS: Cell proliferation was suppressed by knocking down the expression of CD47 in human OSCC cell line Cal-27 cells but there was no change in the apoptosis rate. Moreover, impaired expression of CD47 inhibited the migration and invasion of Cal-27 cells. Furthermore, we found that nude mice injected with CD47 knockeddown Cal-27 cells displayed decreased tumor volumes at week 9 compared to xenograft transplantations of blank Cal-27 cells. In addition, in vitro phagocytosis of Cal-27 cells by macrophages was significantly enhanced after the knockdown of CD47, which positively correlated with compromised STAT3/JAK2 signaling. CONCLUSION: In summary, the knockdown of CD47 downregulated the development of OSCC and increased the phagocytosis of Cal-27 cells, indicating that CD47 might be a promising therapeutic target.