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1.
Int J Mol Sci ; 23(2)2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35055069

RESUMO

The oral cavity is inhabited by a wide spectrum of microbial species, and their colonization is mostly based on commensalism. These microbes are part of the normal oral flora, but there are also opportunistic species that can cause oral and systemic diseases. Although there is a strong exposure to various microorganisms, the oral mucosa reduces the colonization of microorganisms with high rotation and secretion of various types of cytokines and antimicrobial proteins such as defensins. In some circumstances, the imbalance between normal oral flora and pathogenic flora may lead to a change in the ratio of commensalism to parasitism. Healthy oral mucosa has many important functions. Thanks to its integrity, it is impermeable to most microorganisms and constitutes a mechanical barrier against their penetration into tissues. Our study aims to present the role and composition of the oral cavity microbiota as well as defense mechanisms within the oral mucosa which allow for maintaining a balance between such numerous species of microorganisms. We highlight the specific aspects of the oral mucosa protecting barrier and discuss up-to-date information on the immune cell system that ensures microbiota balance. This study presents the latest data on specific tissue stimuli in the regulation of the immune system with particular emphasis on the resistance of the gingival barrier. Despite advances in understanding the mechanisms regulating the balance on the microorganism/host axis, more research is still needed on how the combination of these diverse signals is involved in the regulation of immunity at the oral mucosa barrier.


Assuntos
Interações entre Hospedeiro e Microrganismos/imunologia , Imunidade nas Mucosas , Microbiota/imunologia , Mucosa Bucal/imunologia , Mucosa Bucal/microbiologia , Fatores Etários , Animais , Autoimunidade , Biodiversidade , Suscetibilidade a Doenças , Disbiose , Humanos , Simbiose
2.
Sci Rep ; 12(1): 1162, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-35064144

RESUMO

Oral lichen planus (OLP) is a localized autoimmune disease of the oral mucosa, with an incidence of up to 2%. Although corticosteroids are the first-line treatment, they cause several adverse effects. Quercetin, a naturally occurring compound, has fewer side-effects and provides long-term benefits. Besides, it has powerful anti­inflammatory activities. Here, we combined network pharmacology with experimental verification to predict and verify the key targets of quercetin against OLP. First, 66 quercetin-OLP common targets were analyzed from various databases. The protein-protein interaction (PPI) network was constructed. Topology analysis and MCODE cluster analysis of common targets were conducted to identify 12 key targets including TP53, IL-6 and IFN-γ and their connections. Gene functions and key signaling pathways, including reactive oxygen species metabolism, IL-17 pathway and AGE-RAGE pathway, were enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, in vitro experiments showed that quercetin interfered with Th1/Th2 balance by acting on IL-6 and IFN-γ to modulate the immune system in treating OLP. Quercetin considerably affected the apoptosis and migration of T lymphocytes in OLP patients. Our study reveals the potential therapeutic targets and signaling pathways of quercetin associated with OLP, and establishes the groundwork for future clinical applications.


Assuntos
Líquen Plano Bucal/tratamento farmacológico , Mucosa Bucal/efeitos dos fármacos , Quercetina/farmacologia , Linfócitos T/efeitos dos fármacos , Adulto , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Feminino , Redes Reguladoras de Genes/efeitos dos fármacos , Redes Reguladoras de Genes/imunologia , Voluntários Saudáveis , Humanos , Líquen Plano Bucal/imunologia , Líquen Plano Bucal/patologia , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Cultura Primária de Células , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/efeitos dos fármacos , Mapas de Interação de Proteínas/genética , Mapas de Interação de Proteínas/imunologia , Quercetina/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Linfócitos T/imunologia , Equilíbrio Th1-Th2/efeitos dos fármacos
3.
Bull Exp Biol Med ; 172(2): 158-163, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34855089

RESUMO

In postnatal ontogeny, the topographic relationships of the tongue glands and lymphoid structures in the thickness of the tongue have clear age-related features. In this article, we discuss the features of the glandular-lymphoid relationship in the thickness of the tongue, which is of particular scientific and practical importance for more precise understanding of the mechanisms providing local immunity in the oral cavity.


Assuntos
Tecido Linfoide/imunologia , Mucosa Bucal/imunologia , Língua/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Criança , Pré-Escolar , Feminino , Humanos , Imunidade Inata/fisiologia , Lactente , Recém-Nascido , Tecido Linfoide/patologia , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Glândulas Salivares/imunologia , Glândulas Salivares/patologia , Língua/patologia , Adulto Jovem
4.
Sci Rep ; 11(1): 23789, 2021 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-34893669

RESUMO

Genetics (i.e., mutations) has been assumed to be the major factor in rheumatoid arthritis (RA) etiology, but accounts for a minority of the variance in disease risk for RA. In contrast to genetics, the environment can have dramatic impacts on epigenetics that associate with disease etiology. The current study used buccal cells and purified blood monocytes from two different clinical cohorts involving Caucasian or African American female populations with or without arthritis. The differential DNA methylation regions (DMRs) between the control and RA populations were identified with an epigenome-wide association study. The DMRs (i.e., epimutations) identified in the buccal cells and monocytes were found to be distinct. The DMR associated genes were identified and many have previously been shown to be associated with arthritis. Observations demonstrate DNA methylation epimutation RA biomarkers are cell type specific and similar findings were observed with the two racial background populations. Rheumatoid arthritis susceptibility epigenetic diagnosis appears feasible and may improve the clinical management of RA and allowpreventative medicine considerations.


Assuntos
Artrite Reumatoide/etiologia , Biomarcadores , Metilação de DNA , Epigênese Genética , Epigenômica , Monócitos/metabolismo , Mucosa Bucal/metabolismo , Adulto , Idoso , Autoimunidade/genética , Biologia Computacional/métodos , Suscetibilidade a Doenças , Epigenômica/métodos , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Pessoa de Meia-Idade , Monócitos/imunologia , Mucosa Bucal/imunologia , Fatores Sexuais
5.
Front Immunol ; 12: 768397, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34925337

RESUMO

Approximately 9 out of 10 adults have some form of periodontal disease, an infection-induced inflammatory disease of the tooth-supporting tissues. The initial form, gingivitis, often remains asymptomatic, but this can evolve into periodontitis, which is typically associated with halitosis, oral pain or discomfort, and tooth loss. Furthermore, periodontitis may contribute to systemic disorders like cardiovascular disease and type 2 diabetes mellitus. Control options remain nonspecific, time-consuming, and costly; largely relying on the removal of dental plaque and calculus by mechanical debridement. However, while dental plaque bacteria trigger periodontal disease, it is the host-specific inflammatory response that acts as main driver of tissue destruction and disease progression. Therefore, periodontal disease control should aim to alter the host's inflammatory response as well as to reduce the bacterial triggers. Vaccines may provide a potent adjunct to mechanical debridement for periodontal disease prevention and treatment. However, the immunopathogenic complexity and polymicrobial aspect of PD appear to complicate the development of periodontal vaccines. Moreover, a successful periodontal vaccine should induce protective immunity in the oral cavity, which proves difficult with traditional vaccination methods. Recent advances in mucosal vaccination may bridge the gap in periodontal vaccine development. In this review, we offer a comprehensive overview of mucosal vaccination strategies to induce protective immunity in the oral cavity for periodontal disease control. Furthermore, we highlight the need for additional research with appropriate and clinically relevant animal models. Finally, we discuss several opportunities in periodontal vaccine development such as multivalency, vaccine formulations, and delivery systems.


Assuntos
Mucosa Bucal/imunologia , Mucosa Nasal/imunologia , Doenças Periodontais/prevenção & controle , Vacinação , Animais , Humanos , Doenças Periodontais/terapia
6.
Front Immunol ; 12: 777858, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956206

RESUMO

Background: Developing an understanding of the antibody response, seroprevalence, and seroconversion from natural infection and vaccination against SARS-CoV-2 will give way to a critical epidemiological tool to predict reinfection rates, identify vulnerable communities, and manage future viral outbreaks. To monitor the antibody response on a larger scale, we need an inexpensive, less invasive, and high throughput method. Methods: Here we investigate the use of oral mucosal fluids from individuals recovered from SARS-CoV-2 infection to monitor antibody response and persistence over a 12-month period. For this cohort study, enzyme-linked immunosorbent assays (ELISAs) were used to quantify anti-Spike(S) protein IgG antibodies in participants who had prior SARS-CoV-2 infection and regularly (every 2-4 weeks) provided both serum and oral fluid mucosal fluid samples for longitudinal antibody titer analysis. Results: In our study cohort (n=42) with 17 males and 25 females with an average age of 45.6 +/- 19.3 years, we observed no significant change in oral mucosal fluid IgG levels across the time course of antibody monitoring. In oral mucosal fluids, all the participants who initially had detectable antibodies continued to have detectable antibodies throughout the study. Conclusions: Based on the results presented here, we have shown that oral mucosal fluid-based assays are an effective, less invasive tool for monitoring seroprevalence and seroconversion, which offers an alternative to serum-based assays for understanding the protective ability conferred by the adaptive immune response from viral infection and vaccination against future reinfections.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/imunologia , Imunoglobulina G/imunologia , Saliva/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , SARS-CoV-2 , Soroconversão , Glicoproteína da Espícula de Coronavírus/imunologia
7.
Science ; 374(6575): eabl5450, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34941394

RESUMO

Tissue-specific cues are critical for homeostasis at mucosal barriers. Here, we report that the clotting factor fibrin is a critical regulator of neutrophil function at the oral mucosal barrier. We demonstrate that commensal microbiota trigger extravascular fibrin deposition in the oral mucosa. Fibrin engages neutrophils through the αMß2 integrin receptor and activates effector functions, including the production of reactive oxygen species and neutrophil extracellular trap formation. These immune-protective neutrophil functions become tissue damaging in the context of impaired plasmin-mediated fibrinolysis in mice and humans. Concordantly, genetic polymorphisms in PLG, encoding plasminogen, are associated with common forms of periodontal disease. Thus, fibrin is a critical regulator of neutrophil effector function, and fibrin-neutrophil engagement may be a pathogenic instigator for a prevalent mucosal disease.


Assuntos
Fibrina/metabolismo , Mucosa Bucal/imunologia , Mucosa Bucal/metabolismo , Ativação de Neutrófilo , Neutrófilos/imunologia , Periodontite/genética , Plasminogênio/genética , Perda do Osso Alveolar , Animais , Armadilhas Extracelulares/metabolismo , Feminino , Fibrina/química , Fibrinogênio/metabolismo , Fibrinolisina/metabolismo , Fibrinólise , Microbioma Gastrointestinal/fisiologia , Gengiva/imunologia , Humanos , Imunidade nas Mucosas , Antígeno de Macrófago 1/metabolismo , Masculino , Camundongos , Mucosa Bucal/microbiologia , Periodontite/imunologia , Plasminogênio/deficiência , Plasminogênio/metabolismo , Polimorfismo de Nucleotídeo Único , RNA-Seq , Espécies Reativas de Oxigênio/metabolismo
8.
Int J Mol Sci ; 22(22)2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34830032

RESUMO

The oral mucosa is a site of intense immune activity, where a large variety of immune cells meet to provide a first line of defense against pathogenic organisms. Interestingly, the oral mucosa is exposed to a plethora of antigens from food and commensal bacteria that must be tolerated. The mechanisms that enable this tolerance are not yet fully defined. Many works have focused on active immune mechanisms involving dendritic and regulatory T cells. However, epithelial cells also make a major contribution to tolerance by influencing both innate and adaptive immunity. Therefore, the tolerogenic mechanisms concurring in the oral mucosa are intertwined. Here, we review them systematically, paying special attention to the role of oral epithelial cells.


Assuntos
Imunidade Adaptativa , Células Epiteliais/imunologia , Tolerância Imunológica , Imunidade nas Mucosas , Mucosa Bucal/imunologia , Linfócitos T Reguladores/imunologia , Animais , Humanos
9.
MAbs ; 13(1): 1987180, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34693867

RESUMO

The global health crisis and economic tolls of COVID-19 necessitate a panoply of strategies to treat SARS-CoV-2 infection. To date, few treatment options exist, although neutralizing antibodies against the spike glycoprotein have proven to be effective. Because infection is initiated at the mucosa and propagates mainly at this site throughout the course of the disease, blocking the virus at the mucosal milieu should be effective. However, administration of biologics to the mucosa presents a substantial challenge. Here, we describe bifunctional molecules combining single-domain variable regions that bind to the polymeric Ig receptor (pIgR) and to the SARS-CoV-2 spike protein via addition of the ACE2 extracellular domain (ECD). The hypothesis behind this design is that pIgR will transport the molecule from the circulation to the mucosal surface where the ACE ECD would act as a decoy receptor for the nCoV2. The bifunctional molecules bind SARS-Cov-2 spike glycoprotein in vitro and efficiently transcytose across the lung epithelium in human tissue-based analyses. Designs featuring ACE2 tethered to the C-terminus of the Fc do not induce antibody-dependent cytotoxicity against pIgR-expressing cells. These molecules thus represent a potential therapeutic modality for systemic administration of neutralizing anti-SARS-CoV-2 molecules to the mucosa.


Assuntos
Anticorpos Antivirais , COVID-19/tratamento farmacológico , Receptores de Imunoglobulina Polimérica , SARS-CoV-2/imunologia , Anticorpos de Cadeia Única , Glicoproteína da Espícula de Coronavírus/imunologia , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/imunologia , Animais , Anticorpos Antivirais/genética , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/farmacologia , Células CHO , COVID-19/genética , COVID-19/imunologia , Cricetulus , Cães , Feminino , Humanos , Células Madin Darby de Rim Canino , Camundongos , Mucosa Bucal/imunologia , Domínios Proteicos , Receptores de Imunoglobulina Polimérica/genética , Receptores de Imunoglobulina Polimérica/imunologia , Receptores de Imunoglobulina Polimérica/uso terapêutico , SARS-CoV-2/genética , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/farmacocinética , Anticorpos de Cadeia Única/farmacologia , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Glicoproteína da Espícula de Coronavírus/genética , Suínos
10.
Front Immunol ; 12: 748851, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659248

RESUMO

Type 3 Innate lymphoid cells (ILC3s) have been described as tissue-resident cells and characterized throughout the body, especially in mucosal sites and classical first barrier organs such as skin, gut and lungs, among others. A significant part of the research has focused on their role in combating pathogens, mainly extracellular pathogens, with the gut as the principal organ. However, some recent discoveries in the field have unveiled their activity in other organs, combating intracellular pathogens and as part of the response to viruses. In this review we have compiled the latest studies on the role of ILC3s and the molecular mechanisms involved in defending against different microbes at the mucosal surface, most of these studies have made use of conditional transgenic mice. The present review therefore attempts to provide an overview of the function of ILC3s in infections throughout the body, focusing on their specific activity in different organs.


Assuntos
Interações Hospedeiro-Patógeno , Linfócitos/imunologia , Animais , Trato Gastrointestinal/imunologia , Humanos , Imunidade Inata , Infecções/imunologia , Pulmão/citologia , Pulmão/imunologia , Mucosa Bucal/citologia , Mucosa Bucal/imunologia , Pele/citologia , Pele/imunologia
11.
STAR Protoc ; 2(4): 100790, 2021 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-34622218

RESUMO

The oral mucosa is an important site for virus infection and transmission, yet few animal models exist to examine the virology, pathology, and immunology of acute oral mucosal viral infection. Here, we provide a protocol for infecting and imaging the inner lip (labial mucosa) of mice with the poxvirus vaccinia virus (VACV). Inoculation of the labial mucosa with a bifurcated needle results in viral replication and priming of an adaptive antiviral response that can be imaged using intravital microscopy. For complete details on the use and execution of this protocol, please refer to Shannon et al. (2021).


Assuntos
Antivirais/farmacologia , Modelos Animais de Doenças , Mucosa Bucal , Infecções por Poxviridae , Vírus Vaccinia/efeitos dos fármacos , Animais , Feminino , Camundongos , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/imunologia , Mucosa Bucal/virologia , Infecções por Poxviridae/imunologia , Infecções por Poxviridae/virologia
12.
Nat Commun ; 12(1): 5143, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446704

RESUMO

Residual systemic inflammation and mucosal immune dysfunction persist in people living with HIV, despite treatment with combined anti-retroviral therapy, but the underlying immune mechanisms are poorly understood. Here we report that the altered immune landscape of the oral mucosa of HIV-positive patients on therapy involves increased TLR and inflammasome signaling, localized CD4+ T cell hyperactivation, and, counterintuitively, enrichment of FOXP3+ T cells. HIV infection of oral tonsil cultures in vitro causes an increase in FOXP3+ T cells expressing PD-1, IFN-γ, Amphiregulin and IL-10. These cells persist even in the presence of anti-retroviral drugs, and further expand when stimulated by TLR2 ligands and IL-1ß. Mechanistically, IL-1ß upregulates PD-1 expression via AKT signaling, and PD-1 stabilizes FOXP3 and Amphiregulin through a mechanism involving asparaginyl endopeptidase, resulting in FOXP3+ cells that are incapable of suppressing CD4+ T cells in vitro. The FOXP3+ T cells that are abundant in HIV-positive patients are phenotypically similar to the in vitro cultured, HIV-responsive FOXP3+ T cells, and their presence strongly correlates with CD4+ T cell hyper-activation. This suggests that FOXP3+ T cell dysregulation might play a role in the mucosal immune dysfunction of HIV patients on therapy.


Assuntos
Anfirregulina/imunologia , Fatores de Transcrição Forkhead/imunologia , Infecções por HIV/imunologia , Mucosa Bucal/imunologia , Receptor de Morte Celular Programada 1/imunologia , Linfócitos T/imunologia , Anfirregulina/genética , Linfócitos T CD4-Positivos/imunologia , Fatores de Transcrição Forkhead/genética , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Ativação Linfocitária , Receptor de Morte Celular Programada 1/genética
13.
Biomolecules ; 11(8)2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34439831

RESUMO

Wound healing is an essential process to restore tissue integrity after trauma. Large skin wounds such as burns often heal with hypertrophic scarring and contractures, resulting in disfigurements and reduced joint mobility. Such adverse healing outcomes are less common in the oral mucosa, which generally heals faster compared to skin. Several studies have identified differences between oral and skin wound healing. Most of these studies however focus only on a single stage of wound healing or a single cell type. The aim of this review is to provide an extensive overview of wound healing in skin versus oral mucosa during all stages of wound healing and including all cell types and molecules involved in the process and also taking into account environmental specific factors such as exposure to saliva and the microbiome. Next to intrinsic properties of resident cells and differential expression of cytokines and growth factors, multiple external factors have been identified that contribute to oral wound healing. It can be concluded that faster wound closure, the presence of saliva, a more rapid immune response, and increased extracellular matrix remodeling all contribute to the superior wound healing and reduced scar formation in oral mucosa, compared to skin.


Assuntos
Matriz Extracelular/imunologia , Microbiota/imunologia , Mucosa Bucal/lesões , Pele/lesões , Cicatrização/imunologia , Animais , Citocinas/genética , Citocinas/imunologia , Matriz Extracelular/química , Fibroblastos/imunologia , Fibroblastos/microbiologia , Regulação da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Queratinócitos/imunologia , Queratinócitos/microbiologia , Macrófagos/imunologia , Macrófagos/microbiologia , Mucosa Bucal/imunologia , Mucosa Bucal/microbiologia , Mucosa Bucal/patologia , Neutrófilos/imunologia , Neutrófilos/microbiologia , Especificidade de Órgãos , Saliva/imunologia , Saliva/microbiologia , Transdução de Sinais , Pele/imunologia , Pele/microbiologia , Pele/patologia
14.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34360589

RESUMO

The oral mucosa, which is the lining tissue of the oral cavity, is a gateway to the body and it offers first-line protection against potential pathogens, exogenous chemicals, airborne allergens, etc. by means of its physical and microbiological-immune barrier functions. For this reason, oral mucosa is considered as a mirror to the health of the individual as well as a guard or early warning system. It is organized in two main components: a physical barrier, which consists of stratified epithelial cells and cell-cell junctions, and a microbiological-immune barrier that keeps the internal environment in a condition of homeostasis. Different factors, including microorganism, saliva, proteins and immune components, have been considered to play a critical role in disruption of oral epithelial barrier. Altered mucosal structure and barrier functions results in oral pathologies as well as systemic diseases. About 700 kinds of microorganisms exist in the human mouth, constituting the oral microbiota, which plays a significant role on the induction, training and function of the host immune system. The immune system maintains the symbiotic relationship of the host with this microbiota. Crosstalk between the oral microbiota and immune system includes various interactions in homeostasis and disease. In this review, after reviewing briefly the physical barriers of oral mucosa, the fundamentals of oral microbiome and oral mucosal immunity in regard to their barrier properties will be addressed. Furthermore, their importance in development of new diagnostic, prophylactic and therapeutic strategies for certain diseases as well as in the application for personalized medicine will be discussed.


Assuntos
Homeostase , Imunidade nas Mucosas/imunologia , Microbiota , Mucosa Bucal/imunologia , Mucosa Bucal/microbiologia , Animais , Humanos
15.
Biochim Biophys Acta Mol Basis Dis ; 1867(11): 166217, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34273529

RESUMO

Peri-implantitis could lead to progressive bone loss and implant failure; however, the mechanism of peri-implantitis remains unclear. Based on emerging evidence, pyroptosis, a novel proinflammatory programmed death, contributes to different oral infectious diseases. In the present study, we investigated the involvement of cleaved caspase-3 and gasdermin E (GSDME) in peri-implantitis and established a pyroptosis model in vitro. By collecting and examining the inflamed biopsies around peri-implantitis, we found that the pyroptosis-related markers (caspase-3, GSDME, and IL-1ß) were enhanced relative to levels in control individuals. Furthermore, human gingival epithelium cells (HGECs) induced by tumor necrosis factor-α (TNF-α) exhibited pyroptosis morphological changes (cell swelling and balloon-shaped bubbles) and upregulated expression of pyroptosis-related markers. Pretreated with Ac-DEVD-CHO (a caspase-3 inhibitor) or GSDME small interference RNA (siRNA) were found to attenuate pyroptosis in HGECs. In conclusion, our findings revealed a high expression of caspase-3 and GSDME in the inflamed biopsies of peri-implantitis and confirmed that the caspase-3/GSDME pathway mediates TNF-α-triggered pyroptosis in human gingival epithelium cells, which provides a new target for peri-implantitis treatment.


Assuntos
Caspase 3/metabolismo , Gengiva/patologia , Mucosa Bucal/patologia , Peri-Implantite/imunologia , Receptores de Estrogênio/metabolismo , Biópsia , Estudos de Casos e Controles , Caspase 3/análise , Linhagem Celular , Células Epiteliais , Gengiva/imunologia , Voluntários Saudáveis , Humanos , Mucosa Bucal/imunologia , Peri-Implantite/patologia , Piroptose/imunologia , Receptores de Estrogênio/análise
16.
Front Immunol ; 12: 705206, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290715

RESUMO

Different body systems (epidermis, respiratory tract, cornea, oral cavity, and gastrointestinal tract) are in continuous direct contact with innocuous and/or potentially harmful external agents, exhibiting dynamic and highly selective interaction throughout the epithelia, which function as both a physical and chemical protective barrier. Resident immune cells in the epithelia are constantly challenged and must distinguish among antigens that must be either tolerated or those to which a response must be mounted for. When such a decision begins to take place in lymphoid foci and/or mucosa-associated lymphoid tissues, the epithelia network of immune surveillance actively dominates both oral and gastrointestinal compartments, which are thought to operate in the same immune continuum. However, anatomical variations clearly differentiate immune processes in both the mouth and gastrointestinal tract that demonstrate a wide array of independent immune responses. From single vs. multiple epithelia cell layers, widespread cell-to-cell junction types, microbial-associated recognition receptors, dendritic cell function as well as related signaling, the objective of this review is to specifically contrast the current knowledge of oral versus gut immune niches in the context of epithelia/lymphoid foci/MALT local immunity and systemic output. Related differences in 1) anatomy 2) cell-to-cell communication 3) antigen capture/processing/presentation 4) signaling in regulatory vs. proinflammatory responses and 5) systemic output consequences and its relations to disease pathogenesis are discussed.


Assuntos
Alostase , Homeostase , Imunidade nas Mucosas/imunologia , Vigilância Imunológica/imunologia , Mucosa Intestinal/imunologia , Mucosa Bucal/imunologia , Imunidade Adaptativa , Animais , Apresentação do Antígeno , Translocação Bacteriana/imunologia , Moléculas de Adesão Celular/fisiologia , Comunicação Celular , Células Dendríticas/imunologia , Disbiose/imunologia , Células Epiteliais/imunologia , Humanos , Inflamação , Junções Intercelulares/fisiologia , Mucosa Intestinal/citologia , Microbiota , Mucosa Bucal/citologia , Muco/fisiologia , Especificidade de Órgãos , Saliva/imunologia , Transdução de Sinais
17.
J Immunol Res ; 2021: 9975423, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239944

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC) constitutes the most common types of oral cancer. Because its prognosis varies significantly, identification of a tumor immune microenvironment could be a critical tool for treatment planning and predicting a more accurate prognosis. This study is aimed at utilizing the Hyperion imaging system to depict a preliminary landscape of the tumor immune microenvironment in OSCC with lymph node metastasis. METHODS: We collected neoplasm samples from OSCC patients. Their formalin-fixed, paraffin-embedded (FFPE) tissue sections were obtained and stained utilizing a panel of 26 clinically relevant metal-conjugated antibodies. Detection and analysis were performed for these stained cells with the Hyperion imaging system. RESULTS: Four patients met our inclusion criteria. We depicted a preliminary landscape of their tumor immune microenvironment and identified 25 distinct immune cell subsets from these OSCC patients based on phenotypic similarity. All these patients had decreased expression of CD8+ T cells in tumor specimens. Variety in cell subsets was seen, and more immune activated cells were found in patient A and patient B than those in patient C and patient D. Such differences in tumor immune microenvironments can contribute to forecasting of individual prognoses. CONCLUSION: The Hyperion imaging system helped to delineate a preliminary and multidimensional landscape of the tumor immune microenvironment in OSCC with lymph node metastasis and provided insights into the influence of the immune microenvironment in determination of prognoses. These results reveal possible contributory factors behind different prognoses of OSCC patients with lymph node metastasis and provide reference for individual treatment planning.


Assuntos
Citometria de Varredura a Laser/instrumentação , Metástase Linfática/imunologia , Mucosa Bucal/diagnóstico por imagem , Neoplasias Bucais/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Microambiente Tumoral/imunologia , Adulto , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Masculino , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia
18.
Cell ; 184(15): 4090-4104.e15, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34129837

RESUMO

The oral mucosa remains an understudied barrier tissue. This is a site of rich exposure to antigens and commensals, and a tissue susceptible to one of the most prevalent human inflammatory diseases, periodontitis. To aid in understanding tissue-specific pathophysiology, we compile a single-cell transcriptome atlas of human oral mucosa in healthy individuals and patients with periodontitis. We uncover the complex cellular landscape of oral mucosal tissues and identify epithelial and stromal cell populations with inflammatory signatures that promote antimicrobial defenses and neutrophil recruitment. Our findings link exaggerated stromal cell responsiveness with enhanced neutrophil and leukocyte infiltration in periodontitis. Our work provides a resource characterizing the role of tissue stroma in regulating mucosal tissue homeostasis and disease pathogenesis.


Assuntos
Imunidade nas Mucosas , Mucosa Bucal/citologia , Mucosa Bucal/imunologia , Neutrófilos/citologia , Adulto , Células Epiteliais/citologia , Regulação da Expressão Gênica , Predisposição Genética para Doença , Gengiva/patologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Microbiota , Células Mieloides/citologia , Periodontite/genética , Periodontite/imunologia , Periodontite/patologia , Análise de Célula Única , Células Estromais/citologia , Linfócitos T/citologia
19.
Front Immunol ; 12: 649502, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968042

RESUMO

Pemphigus Vulgaris (PV) is a life-threatening autoimmune disease manifested with blisters in the skin and mucosa and caused by autoantibodies against adhesion protein desmoglein-3 (Dsg3) expressed in epithelial membrane linings of these tissues. Despite many studies, the pathogenesis of PV remains incompletely understood. Recently we have shown Dsg3 plays a role in regulating the yes-associated protein (YAP), a co-transcription factor and mechanical sensor, and constraining reactive oxygen species (ROS). This study investigated the effect of PV sera as well as the anti-Dsg3 antibody AK23 on these molecules. We detected elevated YAP steady-state protein levels in PV cells surrounding blisters and perilesional regions and in keratinocytes treated with PV sera and AK23 with concomitant transient ROS overproduction. Cells treated with hydrogen peroxide also exhibited augmented nuclear YAP accompanied by reduction of Dsg3 and α-catenin, a negative regulator of YAP. As expected, transfection of α-catenin-GFP plasmid rendered YAP export from the nucleus evoked by hydrogen peroxide. In addition, suppression of total YAP was observed in hydrogen peroxide treated cells exposed to antioxidants with enhanced cell-cell adhesion being confirmed by decreased fragmentation in the dispase assay compared to hydrogen peroxide treatment alone. On the other hand, the expression of exogenous YAP disrupted intercellular junction assembly. In contrast, YAP depletion resulted in an inverse effect with augmented expression of junction assembly proteins, including Dsg3 and α-catenin capable of abolishing the effect of AK23 on Dsg3 expression. Finally, inhibition of other kinase pathways, including p38MAPK, also demonstrated suppression of YAP induced by hydrogen peroxide. Furthermore, antioxidant treatment of keratinocytes suppressed PV sera-induced total YAP accumulation. In conclusion, this study suggests that oxidative stress coupled with YAP dysregulation attributes to PV blistering, implying antioxidants may be beneficial in the treatment of PV.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Autoanticorpos/metabolismo , Estresse Oxidativo/imunologia , Pênfigo/imunologia , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Autoanticorpos/sangue , Autoanticorpos/imunologia , Estudos de Casos e Controles , Adesão Celular/efeitos dos fármacos , Adesão Celular/imunologia , Linhagem Celular , Desmogleína 3/imunologia , Desmogleína 3/metabolismo , Técnicas de Silenciamento de Genes , Voluntários Saudáveis , Humanos , Queratinócitos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/imunologia , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Estresse Oxidativo/efeitos dos fármacos , Pênfigo/sangue , Pênfigo/tratamento farmacológico , Pênfigo/patologia , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/genética , alfa Catenina/metabolismo
20.
Medicine (Baltimore) ; 100(20): e25955, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011077

RESUMO

RATIONALE: Mucous membrane pemphigoid (MMP) is a rare, autoimmune bullous disease that affects mucosal surfaces and skin. Early and aggressive treatment initiation may be warranted due to the risks of serious complications. However, it can be challenging to make an initial diagnosis. Viral infection such as hepatitis B virus (HBV) infection has been found to be associated with the formation of autoimmune bullous diseases. PATIENT CONCERNS: The patient was a 43-year-old male with gingivitis and recurrent swelling over the neck, cheeks, lips, and eyelids. The patient presented at oral medicine, otolaryngology, plastic surgery, and ophthalmology sequentially, and was later referred to the rheumatology, dermatology, and family medicine departments. Recurrent hemorrhagic bullae on oral mucosa and skin scarring occurred 2 years after the onset of the initial symptoms. DIAGNOSIS: Skin biopsy with direct immunofluorescence was performed under the suspicion of MMP. Lesional hematoxylin and eosin stain and perilesional direct immunofluorescence were consistent with MMP. INTERVENTIONS: Systemic Prednisolone and topical corticosteroid were used to control the disease. OUTCOMES: A flare-up of hepatitis B developed as a result of systemic prednisolone use. The disease went through relapses and remissions. The patient is on low-dose prednisolone (5 mg/day) with a monthly outpatient visit in the family medicine department. LESSONS: It would be useful for medical practitioners in different specialties to be alert of the heterogeneous presentations of MMP. Chronic HBV infection might be a risk factor for MMP. In patients with chronic HBV infection, treatment of MMP must be closely monitored for the risk of reactivation of HBV.


Assuntos
Hepatite B Crônica/complicações , Penfigoide Mucomembranoso Benigno/diagnóstico , Prednisolona/administração & dosagem , Adulto , Biópsia , Relação Dose-Resposta a Droga , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/imunologia , Humanos , Masculino , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Penfigoide Mucomembranoso Benigno/tratamento farmacológico , Penfigoide Mucomembranoso Benigno/imunologia , Penfigoide Mucomembranoso Benigno/patologia , Prednisolona/efeitos adversos , Pele/imunologia , Pele/patologia , Exacerbação dos Sintomas
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