Effects of interleukin-23 on the activation of mucosal-associated invariant T cells from oral lichen planus.

OBJECTIVE: Oral lichen planus (OLP) is a T cell-mediated inflammatory condition in the oral cavity. Mucosal-associated invariant T (MAIT) cells are gaining more relevance in immune diseases because they can be activated by cytokines without T cell receptor stimulation. Herein, we tested the effect of interleukin-23 (IL-23) on the activation status of OLP MAIT cells. METHODS: Peripheral blood mononuclear cells (PBMCs) isolated from OLP patients were stimulated by IL-23 in the absence or presence of phorbol myristate acetate (PMA) and ionomycin. The activation status of MAIT cells was analyzed by flow cytometry after staining for CD3, CD4, CD8, CD161, TCR Vα7.2, and CD69. RESULTS: The fraction of MAIT cells in OLP peripheral blood was approximately 0.38% to 3.97%, and CD8+ subpopulations overwhelmed CD4+ cells. The mean percentages of OLP MAIT cells in PBMCs and CD8+MAIT cells in MAIT cells were approximately 40%. PMA and ionomycin significantly increased CD69 expression on OLP T cells, MAIT cells, and CD8+MAIT cells. Cells with enhanced activation had different responsiveness to exogenous IL-23, showing increased CD69 expression on OLP T cells, decreased CD69 on OLP CD8+MAIT cells, and no significant change on OLP MAIT cells. CONCLUSIONS: IL-23 showed different effects on the activation status of OLP MAIT cells and CD8+MAIT cells.

MAIT cells and their implication in human oral diseases.

OBJECTIVE: Mucosal-associated invariant T (MAIT) cells are unique innate-like T cells that are abundant in humans, accounting for 1-10% of circulating T cells and about 2% of total T cells in human oral cavity. MAIT cells can mount a strong immune response quickly without exogenous antigens and undergo a phenotypic transformation in the development of diseases. They produce cytokines involved in the Th1 and Th17 immune response and cytotoxic proteins, promote the dysfunction of autoreactive B cell and inhibit the function of NK cells. MAIT cells have been widely explored in autoimmune diseases, inflammatory diseases and tumors, and these mechanisms may also be involved in the pathogenesis of some oral diseases, while MAIT cells have not been systematically discussed in oral diseases. METHODS: We searched PubMed/MEDLINE, EMBASE and Microsoft Bing databases to review and analyze relevant literatures on the impact of MAIT cells in the pathogenesis of human oral diseases. CONCLUSION: Collected evidence elucidated the characteristics of MAIT cells and emphasized the potential roles of MAIT cells in oral lichen planus (OLP), chronic graft-versus-host disease (cGVHD), oral squamous cell carcinoma (OSCC), apical periodontitis (AP) and primary Sjogren's syndrome (pSS).

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.

Characterization and function of circulating mucosal-associated invariant T cells and γδT cells in oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory disease with uncertain aetiology. Mucosal-associated invariant T (MAIT) cells and γδT cells are unconventional, innate-like T cells with immunoregulatory capacity. This study aimed to investigate the potential effects of MAIT and γδT cells on the pathogenesis of OLP. METHODS: Circulating MAIT cells and γδT cells were identified using flow cytometry. Surface proteins including CD4, CD8, CD69, CD103, CD49d, programmed death-1 (PD-1) and its ligand PD-L1 were assessed. Cytokines containing interleukin (IL)-4, IL-17, interferon (IFN)-γ, granzyme B and tumour necrosis factor (TNF)-α released by MAIT and γδT cells were measured following PMA and ionomycin stimulation. RESULTS: Circulating MAIT and γδT cells were deficient in OLP. The percentage of CD4+ , CD69+ , CD103+ and PD-1+ MAIT cells was increased in OLP, while that of CD8+ and CD49d+ MAIT cells was decreased. The percentage of CD103+ , PD-1+ and PD-L1+ γδT cells was upregulated in OLP. Both the MAIT and γδT cells in OLP produced less IL-4 than controls. The granzyme B-producing MAIT cells were increased, while γδT cells secreting granzyme B and TNF-α were reduced in OLP. IL-17 and IFN-γ in OLP MAIT and γδT cells were not significantly different from that in controls. The frequency of OLP MAIT cells and the MAIT/γδT rate were positively associated with the disease severity. CONCLUSION: The deficient MAIT and γδT cells expressing functional proteins and releasing cytokines may play an immunoregulatory role 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.

A nonspecific ulcer on upper lip presented as the first and sole sign of syphilis.

Syphilis, a sexually transmitted disease, can be categorized as acquired syphilis and congenital syphilis, manifesting diverse lesions involving multiple sites. Oral manifestations at the primary stage of acquired syphilis are usually characterized by its short period and non-specific varied presentations. And oral ulcers as initial and the only presentation of syphilis oral lesions are infrequent and occur in less than 2% of patients. Because of its transient nature and variable manifestations which could mimic other oral ulcerative lesions, oral syphilis presenting as sole ulceration at early stage can be easily neglected and rather difficult to diagnose. Herein, we report a 35-year-old female patient manifested a sole atypical ulceration on her upper lip for approximately 1 month. We highlighted the importance of early and accurate diagnosis, focused on the characteristics of oral chancre, and gave an insight to the differential diagnoses, which would be enlightening and useful in clinical practice.

Emerging functions and clinical applications of exosomes in human oral diseases.

Exosomes are cell-derived membranous vesicles of endosomal origin secreted by all type of cells and present in various body fluids. Exosomes are enriched in peptides, lipids, and nucleic acids, emerging as vital modulators in intercellular communication. Exosomes are increasingly being evaluated as biomarkers for diagnosis and prognosis of diseases, because the constituents of exosomes could be reprogrammed depending on the states of diseases. These features also make exosomes a research hotspot in oral diseases in recent years. In this review, we outlined the characteristics of exosomes, focused on the differential expressions and altered biological functions of exosomes in oral diseases, including oral squamous cell carcinoma, oral leukoplakia, periodontitis, primary Sjögren's syndrome, oral lichen planus, as well as hand foot and mouth disease. Besides, accumulated evidence documents that it is implementable to consider the natural nanostructured exosomes as a new strategy for disease treatment. Herein, we highlighted the therapeutic potential of exosomes in oral tissue regeneration, oncotherapy, wound healing, and their superiority as therapeutic drug delivery vehicles.

Black pepper and its bioactive constituent piperine: promising therapeutic strategies for oral lichen planus.

Oral lichen planus (OLP) is a common T cell-mediated chronic inflammatory disease with malignant potential and unclear etiology. The present study suggests that antigen-specific mechanisms in which dentritic cells, T lymphocytes and NF-κB signaling pathway play critical roles, are involved in the pathogenesis of OLP. Additionally, it has been indicated that altered expression of cyclooxygenase 2 (COX-2) and imbalanced oxidant-antioxidant status as well as psychological issue may act as promoters to the development of OLP. Therapies for OLP are primarily aimed to control symptoms and a specific cure is not yet available. Black pepper and its principle bioactive compound piperine have been reported to possess remarkable pharmacological activities. Not only has piperine been evidenced to exhibit repressive effects on the maturation of dentritic cells, the proliferation, activation and function of T lymphocytes as well as the NF-κB signaling pathway, but also to suppress the overproduction of COX-2 and weaken the oxidative stress. Furthermore, piperine might be a possible agent for alleviating psychological disorders and preventing carcinogenesis. Given all these into consideration, piperine may be a novel and effective therapeutic strategy for OLP.