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1.
Hamostaseologie ; 41(5): 387-396, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34695855

RESUMO

Hypercoagulability and vascular injury, which characterize morbidity in COVID-19 disease, are frequently observed in the skin. Several pathomechanisms, such as inflammation caused by angiotensin-converting enzyme 2-mediated uptake into endothelial cells or SARS-CoV-2-initiated host immune responses, contribute to microthrombus formation and the appearance of vascular skin lesions. Besides pathophysiologic mechanisms observed in the skin, this review describes the clinical appearance of cutaneous vascular lesions and their association with COVID-19 disease, including acro-ischemia, reticular lesions, and cutaneous small vessel vasculitis. Clinicians need to be aware that skin manifestations may be the only symptom in SARS-CoV-2 infection, and that inflammatory and thrombotic SARS-CoV-2-driven processes observed in multiple organs and tissues appear identically in the skin as well.


Assuntos
COVID-19/complicações , SARS-CoV-2 , Pele/irrigação sanguínea , Enzima de Conversão de Angiotensina 2/fisiologia , Anticorpos Antifosfolipídeos/sangue , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/patologia , COVID-19/patologia , COVID-19/fisiopatologia , Ativação do Complemento , Citocinas/metabolismo , Interações entre Hospedeiro e Microrganismos/imunologia , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Microvasos/imunologia , Microvasos/patologia , Microvasos/fisiopatologia , Pandemias , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Pele/imunologia , Vasculite/etiologia , Vasculite/patologia , Vasculite/fisiopatologia , Internalização do Vírus
2.
Proc Natl Acad Sci U S A ; 118(45)2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34670842

RESUMO

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other pathogens with pandemic potential requires safe, protective, inexpensive, and easily accessible vaccines that can be developed and manufactured rapidly at a large scale. DNA vaccines can achieve these criteria, but induction of strong immune responses has often required bulky, expensive electroporation devices. Here, we report an ultra-low-cost (<1 USD), handheld (<50 g) electroporation system utilizing a microneedle electrode array ("ePatch") for DNA vaccination against SARS-CoV-2. The low cost and small size are achieved by combining a thumb-operated piezoelectric pulser derived from a common household stove lighter that emits microsecond, bipolar, oscillatory electric pulses and a microneedle electrode array that targets delivery of high electric field strength pulses to the skin's epidermis. Antibody responses against SARS-CoV-2 induced by this electroporation system in mice were strong and enabled at least 10-fold dose sparing compared to conventional intramuscular or intradermal injection of the DNA vaccine. Vaccination was well tolerated with mild, transient effects on the skin. This ePatch system is easily portable, without any battery or other power source supply, offering an attractive, inexpensive approach for rapid and accessible DNA vaccination to combat COVID-19, as well as other epidemics.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/imunologia , COVID-19/prevenção & controle , Eletroporação/instrumentação , SARS-CoV-2 , Vacinas de DNA/administração & dosagem , Animais , Vacinas contra COVID-19/genética , Vacinas contra COVID-19/imunologia , Custos e Análise de Custo , Eletroporação/economia , Eletroporação/métodos , Desenho de Equipamento , Feminino , Genes Reporter , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Microeletrodos , Agulhas , Pandemias/prevenção & controle , Estudo de Prova de Conceito , Ratos , Ratos Wistar , Pele/imunologia , Pele/metabolismo , Transfecção , Vacinação/economia , Vacinação/instrumentação , Vacinação/métodos , Vacinas de DNA/genética , Vacinas de DNA/imunologia
3.
Int J Mol Sci ; 22(19)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34639001

RESUMO

The keratinocyte (KC) is the main functional and structural component of the epidermis, the most external layer of the skin that is highly specialized in defense against external agents, prevention of leakage of body fluids and retention of internal water within the cells. Altered epidermal barrier and aberrant KC differentiation are involved in the pathophysiology of several skin diseases, such as atopic dermatitis (AD). AD is a chronic inflammatory disease characterized by cutaneous and systemic immune dysregulation and skin microbiota dysbiosis. Nevertheless, the pathological mechanisms of this complex disease remain largely unknown. In this review, we summarize current knowledge about the participation of the KC in different aspects of the AD. We provide an overview of the genetic predisposing and environmental factors, inflammatory molecules and signaling pathways of the KC that participate in the physiopathology of the AD. We also analyze the link among the KC, the microbiota and the inflammatory response underlying acute and chronic skin AD lesions.


Assuntos
Dermatite Atópica/etiologia , Dermatite Atópica/metabolismo , Queratinócitos/metabolismo , Alelos , Animais , Biomarcadores , Terapia Combinada , Dermatite Atópica/patologia , Dermatite Atópica/terapia , Gerenciamento Clínico , Progressão da Doença , Suscetibilidade a Doenças/imunologia , Predisposição Genética para Doença , Interações entre Hospedeiro e Microrganismos , Humanos , Imunidade Inata , Queratinócitos/imunologia , Microbiota , Pele/imunologia , Pele/metabolismo , Pele/patologia , Fenômenos Fisiológicos da Pele
4.
Nat Commun ; 12(1): 5947, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642338

RESUMO

Systemic sclerosis (SSc) is a chronic multisystem disorder characterized by fibrosis and autoimmunity. Interleukin (IL)-31 has been implicated in fibrosis and T helper (Th) 2 immune responses, both of which are characteristics of SSc. The exact role of IL-31 in SSc pathogenesis is unclear. Here we show the overexpression of IL-31 and IL-31 receptor A (IL-31RA) in dermal fibroblasts (DFs) from SSc patients. We elucidate the dual role of IL-31 in SSc, where IL-31 directly promotes collagen production in DFs and indirectly enhances Th2 immune responses by increasing pro-Th2 cytokine expression in DFs. Furthermore, blockade of IL-31 with anti-IL-31RA antibody significantly ameliorates fibrosis and Th2 polarization in a mouse model of SSc. Therefore, in addition to defining IL-31 as a mediator of fibrosis and Th2 immune responses in SSc, our study provides a rationale for targeting the IL-31/IL-31RA axis in the treatment of SSc.


Assuntos
Fibroblastos/imunologia , Interleucinas/genética , Receptores de Interleucina/genética , Escleroderma Sistêmico/imunologia , Células Th2/imunologia , Adulto , Idoso , Animais , Anticorpos Monoclonais/farmacologia , Colágeno Tipo I/genética , Colágeno Tipo I/imunologia , Modelos Animais de Doenças , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Fibrose , Regulação da Expressão Gênica , Humanos , Interleucina-13/genética , Interleucina-13/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Interleucinas/imunologia , Masculino , Camundongos , Pessoa de Meia-Idade , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Receptores de Interleucina/antagonistas & inibidores , Receptores de Interleucina/imunologia , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/imunologia , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/patologia , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Células Th2/efeitos dos fármacos , Células Th2/patologia
5.
Nat Immunol ; 22(11): 1375-1381, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34663979

RESUMO

Migration of leukocytes from the skin to lymph nodes (LNs) via afferent lymphatic vessels (LVs) is pivotal for adaptive immune responses1,2. Circadian rhythms have emerged as important regulators of leukocyte trafficking to LNs via the blood3,4. Here, we demonstrate that dendritic cells (DCs) have a circadian migration pattern into LVs, which peaks during the rest phase in mice. This migration pattern is determined by rhythmic gradients in the expression of the chemokine CCL21 and of adhesion molecules in both mice and humans. Chronopharmacological targeting of the involved factors abrogates circadian migration of DCs. We identify cell-intrinsic circadian oscillations in skin lymphatic endothelial cells (LECs) and DCs that cogovern these rhythms, as their genetic disruption in either cell type ablates circadian trafficking. These observations indicate that circadian clocks control the infiltration of DCs into skin lymphatics, a process that is essential for many adaptive immune responses and relevant for vaccination and immunotherapies.


Assuntos
Imunidade Adaptativa , Quimiotaxia , Relógios Circadianos , Células Dendríticas/imunologia , Linfonodos/imunologia , Vasos Linfáticos/imunologia , Pele/imunologia , Idoso , Animais , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Células Cultivadas , Quimiocina CCL21/genética , Quimiocina CCL21/metabolismo , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/genética , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/metabolismo , Células Dendríticas/metabolismo , Feminino , Humanos , Linfonodos/metabolismo , Vasos Linfáticos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pele/metabolismo , Fatores de Tempo
6.
Front Immunol ; 12: 654190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497600

RESUMO

Delayed-type drug hypersensitivity reactions (dtDHR) are immune-mediated reactions with skin and visceral manifestations ranging from mild to severe. Clinical care is negatively impacted by a limited understanding of disease pathogenesis. Though T cells are believed to orchestrate disease, the type of T cell and the location and mechanism of T cell activation remain unknown. Resident memory T cells (TRM) are a unique T cell population potentially well situated to act as key mediators in disease pathogenesis, but significant obstacles to defining, identifying, and testing TRM in dtDHR preclude definitive conclusions at this time. Deeper mechanistic interrogation to address these unanswered questions is necessary, as involvement of TRM in disease has significant implications for prediction, diagnosis, and treatment of disease.


Assuntos
Hipersensibilidade a Drogas/etiologia , Hipersensibilidade Tardia/diagnóstico , Hipersensibilidade Tardia/etiologia , Memória Imunológica , Pele/imunologia , Linfócitos T/imunologia , Animais , Suscetibilidade a Doenças , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/metabolismo , Humanos , Hipersensibilidade Tardia/metabolismo , Ativação Linfocitária , Pele/efeitos dos fármacos , Pele/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T/metabolismo
7.
J Immunol ; 207(9): 2223-2234, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34588217

RESUMO

The pathogenesis of allergic contact dermatitis (ACD) requires the activation of Ag-specific T cells, including effector and regulatory T cells. The differentiation and function of these T cells is epigenetically regulated through DNA methylation and histone modifications. However, the roles of altered histone H3K27 methylation in T cells in the development of ACD remain unknown. Two types of histone H3K27 demethylases, Utx and Jmjd3, have been reported in mammals. To determine the role of the histone H3K27 demethylase expression of T cells in the development of ACD, we generated T cell-specific, Utx-deficient (Utx KO) mice or Jmjd3-deficient (Jmjd3 KO) mice. Unlike control mice, Utx KO mice had severer symptoms of ACD, whereas Jmjd3 KO mice showed symptoms identical to those in control mice. In Utx KO mice with ACD, the massive infiltration of myeloid cells, including neutrophils and dendritic cells, has been observed. In addition, the expression of proinflammatory cytokines in CD4+ T cells of the draining lymph nodes (LNs) and in CD8+ T cells of the skin was increased in Utx KO mice, whereas the ratio of Foxp3+ regulatory CD4+ T cells to Foxp3- conventional CD4+ T cells was decreased in both the draining LNs and the skin of Utx KO mice with ACD. Furthermore, Foxp3+ regulatory CD4+ T cells of Utx KO mice with ACD expressed a decreased level of CCR4 (a skin-tropic chemokine receptor) in comparison with control. Thus, in CD4+ T cells, Utx could potentially be involved in the regulation of the pathogenesis of ACD.


Assuntos
Dermatite de Contato/imunologia , Histona Desmetilases/metabolismo , Histonas/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Pele/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/metabolismo , Histona Desmetilases/genética , Histonas/genética , Humanos , Mediadores da Inflamação/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , Camundongos , Camundongos Knockout , Receptores CCR4/metabolismo
8.
Immunity ; 54(10): 2305-2320.e11, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34508661

RESUMO

Langerhans cells (LCs) play a pivotal role in skin homeostasis, and the heterogeneity of LCs has long been considered. In this study, we have identified two steady-state (LC1 and LC2) and two activated LC subsets in the epidermis of human skin and in LCs derived from CD34+ hemopoietic stem cells (HSC-LCs) by utilizing single-cell RNA sequencing and mass cytometry. Analysis of HSC-LCs at multiple time-points during differentiation revealed that EGR1 and Notch signaling were among the top pathways regulating the bifurcation of LC1 and LC2. LC1 were characterized as classical LCs, mainly related to innate immunity and antigen processing. LC2 were similar to monocytes or myeloid dendritic cells, involving in immune responses and leukocyte activation. LC1 remained stable under inflammatory microenvironment, whereas LC2 were prone to being activated and demonstrated elevated expression of immuno-suppressive molecules. We revealed distinct human LC subsets that require different developmental regulation and orchestrate reciprocal functions.


Assuntos
Diferenciação Celular/imunologia , Células de Langerhans/citologia , Células de Langerhans/imunologia , Pele/citologia , Pele/imunologia , Apresentação do Antígeno/imunologia , Células-Tronco Hematopoéticas/imunologia , Humanos , Imunidade Inata/imunologia
9.
Immunity ; 54(10): 2321-2337.e10, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34582748

RESUMO

Hair follicles (HFs) function as hubs for stem cells, immune cells, and commensal microbes, which must be tightly regulated during homeostasis and transient inflammation. Here we found that transmembrane endopeptidase ADAM10 expression in upper HFs was crucial for regulating the skin microbiota and protecting HFs and their stem cell niche from inflammatory destruction. Ablation of the ADAM10-Notch signaling axis impaired the innate epithelial barrier and enabled Corynebacterium species to predominate the microbiome. Dysbiosis triggered group 2 innate lymphoid cell-mediated inflammation in an interleukin-7 (IL-7) receptor-, S1P receptor 1-, and CCR6-dependent manner, leading to pyroptotic cell death of HFs and irreversible alopecia. Double-stranded RNA-induced ablation models indicated that the ADAM10-Notch signaling axis bolsters epithelial innate immunity by promoting ß-defensin-6 expression downstream of type I interferon responses. Thus, ADAM10-Notch signaling axis-mediated regulation of host-microbial symbiosis crucially protects HFs from inflammatory destruction, which has implications for strategies to sustain tissue integrity during chronic inflammation.


Assuntos
Proteína ADAM10/imunologia , Secretases da Proteína Precursora do Amiloide/imunologia , Disbiose/imunologia , Folículo Piloso/patologia , Linfócitos/imunologia , Proteínas de Membrana/imunologia , Receptores Notch/imunologia , Pele/microbiologia , Alopecia/imunologia , Alopecia/patologia , Animais , Corynebacterium , Disbiose/patologia , Feminino , Folículo Piloso/imunologia , Imunidade Inata , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Transdução de Sinais/imunologia , Pele/imunologia , Pele/patologia
10.
Nutrients ; 13(9)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34579088

RESUMO

The incidence of atopic dermatitis (AD), a disease characterized by an abnormal immune balance and skin barrier function, has increased rapidly in developed countries. This study investigated the anti-atopic effect of Lithospermum erythrorhizon (LE) using NC/Nga mice induced by 2,4-dinitrochlorobenzene. LE reduced AD clinical symptoms, including inflammatory cell infiltration, epidermal thickness, ear thickness, and scratching behavior, in the mice. Additionally, LE reduced serum IgE and histamine levels, and restored the T helper (Th) 1/Th2 immune balance through regulation of the IgG1/IgG2a ratio. LE also reduced the levels of AD-related cytokines and chemokines, including interleukin (IL)-1ß, IL-4, IL-6, tumor necrosis factor-α (TNF-α), thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, regulated on activation, normal T cell expressed and secreted, and monocyte chemoattractant protein-1 in the serum. Moreover, LE modulated AD-related cytokines and chemokines expressed and secreted by Th1, Th2, Th17, and Th22 cells in the dorsal skin and splenocytes. Furthermore, LE restored skin barrier function by increasing pro-filaggrin gene expression and levels of skin barrier-related proteins filaggrin, involucrin, loricrin, occludin, and zonula occludens-1. These results suggest that LE is a potential therapeutic agent that can alleviate AD by modulating Th1/Th2 immune balance and restoring skin barrier function.


Assuntos
Dermatite Atópica/tratamento farmacológico , Lithospermum/química , Extratos Vegetais/farmacologia , Pele/efeitos dos fármacos , Pele/patologia , Animais , Benzofuranos/química , Benzofuranos/farmacologia , Citocinas/genética , Citocinas/metabolismo , Depsídeos/química , Depsídeos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Imunoglobulina G/sangue , Imunoglobulina G/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos , Extratos Vegetais/química , Pele/imunologia , Baço/citologia , Equilíbrio Th1-Th2/efeitos dos fármacos
11.
J Immunol ; 207(7): 1763-1775, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470859

RESUMO

Regulatory T cells (Tregs) reside in nonlymphoid tissues where they carry out unique functions. The molecular mechanisms responsible for Treg accumulation and maintenance in these tissues are relatively unknown. Using an unbiased discovery approach, we identified LAYN (layilin), a C-type lectin-like receptor, to be preferentially and highly expressed on a subset of activated Tregs in healthy and diseased human skin. Expression of layilin on Tregs was induced by TCR-mediated activation in the presence of IL-2 or TGF-ß. Mice with a conditional deletion of layilin in Tregs had reduced accumulation of these cells in tumors. However, these animals somewhat paradoxically had enhanced immune regulation in the tumor microenvironment, resulting in increased tumor growth. Mechanistically, layilin expression on Tregs had a minimal effect on their activation and suppressive capacity in vitro. However, expression of this molecule resulted in a cumulative anchoring effect on Treg dynamic motility in vivo. Taken together, our results suggest a model whereby layilin facilitates Treg adhesion in skin and, in doing so, limits their suppressive capacity. These findings uncover a unique mechanism whereby reduced Treg motility acts to limit immune regulation in nonlymphoid organs and may help guide strategies to exploit this phenomenon for therapeutic benefit.


Assuntos
Proteínas de Transporte/metabolismo , Glicoproteínas de Membrana/metabolismo , Receptores de Retorno de Linfócitos/metabolismo , Pele/imunologia , Linfócitos T Reguladores/imunologia , Animais , Proteínas de Transporte/genética , Movimento Celular , Células Cultivadas , Humanos , Tolerância Imunológica , Ativação Linfocitária , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Imunológicos , Especificidade de Órgãos , Receptores de Retorno de Linfócitos/genética , Fator de Crescimento Transformador beta/metabolismo
12.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445108

RESUMO

Atopic dermatitis (AD) is a common inflammatory dermatosis affecting up to 30% of children and 10% of adults worldwide. AD is primarily driven by an epidermal barrier defect which triggers immune dysregulation within the skin. According to recent research such phenomena are closely related to the microbial dysbiosis of the skin. There is growing evidence that cutaneous microbiota and bacterial biofilms negatively affect skin barrier function, contributing to the onset and exacerbation of AD. This review summarizes the latest data on the mechanisms leading to microbiome dysbiosis and biofilm formation in AD, and the influence of these phenomena on skin barrier function.


Assuntos
Bactérias/imunologia , Biofilmes/crescimento & desenvolvimento , Dermatite Atópica/imunologia , Disbiose/imunologia , Epiderme/imunologia , Microbiota/imunologia , Animais , Disbiose/microbiologia , Humanos , Pele/imunologia
13.
Nat Commun ; 12(1): 4700, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34349124

RESUMO

During skin injury, immune response and repair mechanisms have to be coordinated for rapid skin regeneration and the prevention of microbial infections. Natural Killer (NK) cells infiltrate hypoxic skin lesions and Hypoxia-inducible transcription factors (HIFs) mediate adaptation to low oxygen. We demonstrate that mice lacking the Hypoxia-inducible factor (HIF)-1α isoform in NK cells show impaired release of the cytokines Interferon (IFN)-γ and Granulocyte Macrophage - Colony Stimulating Factor (GM-CSF) as part of a blunted immune response. This accelerates skin angiogenesis and wound healing. Despite rapid wound closure, bactericidal activity and the ability to restrict systemic bacterial infection are impaired. Conversely, forced activation of the HIF pathway supports cytokine release and NK cell-mediated antibacterial defence including direct killing of bacteria by NK cells despite delayed wound closure. Our results identify, HIF-1α in NK cells as a nexus that balances antimicrobial defence versus global repair in the skin.


Assuntos
Células Matadoras Naturais/imunologia , Pele/imunologia , Pele/microbiologia , Cicatrização , Animais , Hipóxia Celular , Citocinas/metabolismo , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/patologia , Camundongos , Neovascularização Fisiológica , Pele/irrigação sanguínea , Dermatopatias Bacterianas/prevenção & controle
15.
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
16.
Biomolecules ; 11(8)2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34439900

RESUMO

Hyaluronic acid (HA), a glycosaminoglycan ubiquitous in the skin, has come into the limelight in recent years for its role in facilitating dermal wound healing. Specifically, HA's length of linearly repeating disaccharides-in other words, its molecular weight (MW)-determines its effects. High molecular weight (HMW)-HA serves an immunosuppressive and anti-inflammatory role, whereas low molecular weight (LMW)-HA contributes to immunostimulation and thus inflammation. During the inflammatory stage of tissue repair, direct and indirect interactions between HA and the innate and adaptive immune systems are of particular interest for their long-lasting impact on wound repair. This review seeks to synthesize the literature on wound healing with a focus on HA's involvement in the immune subsystems.


Assuntos
Ácido Hialurônico/química , Pele/imunologia , Pele/patologia , Cicatrização , Imunidade Adaptativa , Animais , Anti-Inflamatórios , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Células Dendríticas/imunologia , Dissacarídeos/química , Glicosaminoglicanos/química , Humanos , Receptores de Hialuronatos/metabolismo , Sistema Imunitário , Imunidade Inata , Imunossupressores , Inflamação , Linfócitos Intraepiteliais/imunologia , Macrófagos/imunologia , Mastócitos/imunologia , Camundongos , Peso Molecular , Pele/metabolismo , Linfócitos T/imunologia
17.
Front Immunol ; 12: 662307, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354699

RESUMO

The treatment of multibacillary cases of leprosy with multidrug therapy (MDT) comprises 12 doses of a combination of rifampicin, dapsone and clofazimine. Previous studies have described the immunological phenotypic pattern in skin lesions in multibacillary patients. Here, we evaluated the effect of MDT on skin cell phenotype and on the Mycobacterium leprae-specific immune response. An analysis of skin cell phenotype demonstrated a significant decrease in MRS1 (SR-A), CXCL10 (IP-10) and IFNG (IFN-γ) gene and protein expression after MDT release. Patients were randomized according to whether they experienced a reduction in bacillary load after MDT. A reduction in CXCL10 (IP-10) in sera was associated with the absence of a reduction in the bacillary load at release. Although IFN-γ production in response to M. leprae was not affected by MDT, CXCL10 (IP-10) levels in response to M. leprae increased in cells from patients who experienced a reduction in bacillary load after treatment. Together, our results suggest that CXCL10 (IP-10) may be a good marker for monitoring treatment efficacy in multibacillary patients.


Assuntos
Quimiocina CXCL10/sangue , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Pele/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carga Bacteriana/efeitos dos fármacos , Biomarcadores/sangue , Quimiocina CXCL10/imunologia , Quimioterapia Combinada , Feminino , Humanos , Hansenostáticos/administração & dosagem , Hanseníase/imunologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/imunologia , Pele/microbiologia , Pele/patologia , Resultado do Tratamento , Adulto Jovem
18.
J Immunol Methods ; 497: 113107, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34352237

RESUMO

Understanding the interplay between immune and structural cells is important for studying fibrosis and inflammation; however, primary immune cell isolation from organs that are typically enriched in stromal cells, like the lung, esophagus, or gut, proves to be an ongoing challenge. In fibrotic conditions, this challenge becomes even greater as infiltrating cells become trapped in the robust extracellular matrix (ECM). This protocol details a method to isolate cells at high yield from stroma-rich organs that can be used for further analyses via flow cytometry, stimulation, or culturing. Validation of this method is confirmed by flow cytometry data assessing immune cell populations of interest. This protocol can be completed in approximately 5-6 h.


Assuntos
Separação Celular , Mucosa Esofágica/citologia , Citometria de Fluxo , Mucosa Intestinal/citologia , Pele/patologia , Animais , Biomarcadores/metabolismo , Sobrevivência Celular , Células Cultivadas , Colagenases/metabolismo , Endopeptidases/metabolismo , Mucosa Esofágica/imunologia , Mucosa Esofágica/metabolismo , Fibrose , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Camundongos Endogâmicos C57BL , Pele/imunologia , Pele/metabolismo , Fatores de Tempo , Tripsina/metabolismo , Fluxo de Trabalho
19.
Sci Rep ; 11(1): 16091, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373514

RESUMO

Cold atmospheric plasma (CAP) has been incorporated into various fields, including promotion of cutaneous wound healing. Atopic dermatitis (AD) is a chronic cutaneous condition characterized by inflammation-induced skin wounds and impaired skin barrier function. To investigate whether CAP may improve AD using an animal model. Dermatophagoides farinae extracts (DFE)-induced murine models of AD were used in this study. The plasma-treated group received a total of 6 CAP treatments during 2 weeks, while the control group did not receive any treatment. Differences in dermatitis severity, transepidermal water loss (TEWL), serum level of immunoglobulin (Ig) E and epidermal thickness were evaluated in both groups. The dermatitis severity was significantly improved by CAP treatment. TEWL was lower in the plasma-treated group compared with the non-treated control group. Serum Ig E dropped significantly after treatment with CAP. Difference in epidermal thickness of the ear skin was not significant between the plasma-treated and non-treated groups. Localized treatment of AD with CAP decreases dermatitis severity, TEWL, and serum Ig E level. These results show CAP's potentials as a novel therapeutic modality for AD.


Assuntos
Dermatite Atópica/imunologia , Dermatite Atópica/terapia , Animais , Dermatophagoides farinae/imunologia , Modelos Animais de Doenças , Epiderme/imunologia , Imunoglobulina E/imunologia , Inflamação/imunologia , Inflamação/terapia , Masculino , Camundongos , Pele/imunologia
20.
Front Immunol ; 12: 688861, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335591

RESUMO

Psoriasis (PsO) is a common T cell-mediated inflammatory disorder of the skin with an estimated prevalence of 2%. The condition manifests most commonly as erythematous plaques covered with scales. The aetiology of PsO is multifactorial and disease initiation involves interactions between environmental factors, susceptibility genes, and innate and adaptive immune responses. The underlying pathology is mainly driven by interleukin-17. In addition, various inflammatory mediators from specific T helper (TH) cell subsets, namely TH1, TH17, and TH22, are overexpressed in cutaneous lesions and may also be detected in the peripheral blood of psoriatic patients. Moreover, these individuals are also at greater risk, compared to the general population, of developing multiple comorbid conditions. Cardiovascular disease (CVD) has been recognised as a prominent comorbidity of PsO. A potential mechanism contributing to this association may be the presence of a hypercoagulable state in these individuals. Inflammation and coagulation are closely related. The presence of chronic, low-grade systemic inflammation may promote thrombosis - one of the major determinants of CVD. A pro-inflammatory milieu may induce the expression of tissue factor, augment platelet activity, and perturb the vascular endothelium. Altogether, these changes will result in a prothrombotic state. In this review, we describe the aetiology of PsO, as well as the pathophysiology of the condition. We also consider its relationship to CVD. Given the systemic inflammatory nature of PsO, we evaluate the potential contribution of prominent inflammatory mediators (implicated in PsO pathogenesis) to establishing a prothrombotic state in psoriatic patients.


Assuntos
Coagulação Sanguínea , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Psoríase/complicações , Pele/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Trombose/etiologia , Animais , Anti-Inflamatórios/uso terapêutico , Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/prevenção & controle , Fatores de Risco de Doenças Cardíacas , Humanos , Prognóstico , Psoríase/sangue , Psoríase/tratamento farmacológico , Psoríase/imunologia , Medição de Risco , Pele/efeitos dos fármacos , Pele/imunologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/imunologia , Trombose/sangue , Trombose/tratamento farmacológico , Trombose/imunologia
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