Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.202
Filtrar
1.
Science ; 376(6596): 940-945, 2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35617415

RESUMO

Human skin forms a protective barrier against the external environment and is our first line of defense against toxic, solar, and pathogenic insults. Our skin also defines our outward appearance, protects our internal tissues and organs, acts as a sensory interface, and prevents dehydration. Crucial to the skin's barrier function is the colonizing microbiota, which provides protection against pathogens, tunes immune responses, and fortifies the epithelium. Here we highlight recent advances in our understanding of how the microbiota mediates multiple facets of skin barrier function. We discuss recent insights into pathological host-microbiota interactions and implications for disorders of the skin and distant organs. Finally, we examine how microbiota-based mechanisms can be targeted to prevent or manage skin disorders and impaired wound healing.


Assuntos
Interações entre Hospedeiro e Microrganismos , Microbiota , Pele , Epitélio/imunologia , Epitélio/microbiologia , Folículo Piloso/imunologia , Folículo Piloso/microbiologia , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Pele/imunologia , Pele/microbiologia , Dermatopatias/imunologia , Dermatopatias/terapia , Cicatrização/imunologia
2.
Vet Immunol Immunopathol ; 246: 110401, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35255296

RESUMO

A more complete understanding of canine T-lymphocyte immunity is necessary for improving diagnostic and therapeutic approaches to canine diseases, developing cell-based canine immunotherapeutics, and evaluating dogs as large mammal models for comparative immunology research. The aim of this study was to utilize CD45RA (indicating antigen inexperience) and CD62L (indicating lymph node homing capability), to quantify canine memory T-cell subsets in healthy dogs and dogs with various diseases. Peripheral blood mononuclear cells (PBMCs) were prospectively collected from dogs belonging to one of four groups:dermatologic inflammation (n = 9), solid tumors (n = 9), lymphoma (n = 9), and age-/weight-matched healthy control dogs (n = 15). Dogs receiving prednisone or any other immunomodulating medication within two weeks were excluded. Flow cytometry was performed and T-cell subsets were defined as CD4+ or CD8+, and naïve (TN), central memory (CM), effector memory (EM), or terminal effector memory re-expressing CD45RA (TEMRA). T-cell subset proportions were compared between each disease group and their healthy age-/weight-matched controls using a Mann-Whitney test. Significantly increased %CD8+ TN (P = 0.036) and decreased %CD8+ TEMRA (P = 0.045) were detected in dogs with dermatologic inflammation compared to healthy controls. Furthermore, %CD4+ TN positively correlated with Canine Atopic Dermatitis Extent and Severity Index (CADESI) score within the inflammation group (ρ = 0.817, P = 0.011). No significant differences between either cancer group and their healthy controls were detected. Taken together, these data indicate that dermatologic inflammation can alter proportions of peripheral blood T-cell subsets, possibly due to the migration of antigen-specific T-cells into tissues. Furthermore, these findings support the utility of CD45RA and CD62L in characterizing clinical canine immune responses.


Assuntos
Doenças do Cão , Memória Imunológica , Dermatopatias , Animais , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Doenças do Cão/imunologia , Cães , Selectina L , Antígenos Comuns de Leucócito , Leucócitos Mononucleares , Neoplasias/imunologia , Neoplasias/veterinária , Dermatopatias/imunologia , Dermatopatias/veterinária
3.
J Leukoc Biol ; 111(2): 301-312, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34730257

RESUMO

Deficiency of adenosine deaminase 2 (DADA2) is a monogenic vasculitis syndrome caused by autosomal-recessive loss-of-function mutations in the ADA2 gene (previously known as CECR1). Vasculitis, vasculopathy, and inflammation are dominant clinical features of this disease; the spectrum of manifestations includes immunodeficiency and lymphoproliferation as well as hematologic manifestations. ADA2 is primarily secreted by stimulated monocytes and macrophages. Aberrant monocyte differentiation to macrophages and neutrophils are important in the pathogenesis of DADA2, but little is known about T lymphocytes in this disease. We performed combined single-cell RNA sequencing and single-cell TCR sequencing in order to profile T cell repertoires in 10 patients with DADA2. Although there were no significant alterations of T cell subsets, we observed activation of both CD8+ and CD4+ T cells. There was no clonal expansion of T cells: most TCRs were expressed at basal levels in patients and healthy donors. TCR usage was private to individual patients and not disease specific, indicating as unlikely a common pathogenic background or predisposition to a common pathogen. We recognized activation of IFN pathways as a signature of T cells and STAT1 as a hub gene in the gene network of T cell activation and cytotoxicity. Overall, T cells in DADA2 patients showed distinct cell-cell interactions with monocytes, as compared with healthy donors, and many of these ligand-receptor interactions likely drove up-regulation of STAT1 in both T cells and other immune cells in patients. Our analysis reveals previously undercharacterized cell characteristics in DADA2.


Assuntos
Adenosina Desaminase/deficiência , Biomarcadores/metabolismo , Regulação da Expressão Gênica , Síndromes de Imunodeficiência/patologia , Peptídeos e Proteínas de Sinalização Intercelular/deficiência , Dermatopatias/patologia , Linfócitos T/patologia , Doenças Vasculares/patologia , Adenosina Desaminase/genética , Adolescente , Adulto , Estudos de Casos e Controles , Células Cultivadas , Criança , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Fator de Transcrição STAT1/genética , Análise de Célula Única , Dermatopatias/genética , Dermatopatias/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Doenças Vasculares/genética , Doenças Vasculares/imunologia , Adulto Jovem
4.
J Cutan Med Surg ; 26(1): 33-49, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34261335

RESUMO

Type 2 immunity, illustrated by T helper 2 lymphocytes (Th2) and downstream cytokines (IL-4, IL-13, IL-31) as well as group 2 innate lymphoid cells (ILC2), is important in host defense and wound healing.1 The hallmark of type 2 inflammation is eosinophilia and/or high IgE counts and is best recognized in atopic diathesis. Persistent eosinophilia, such as seen in hypereosinophilic syndromes, leads to fibrosis and hence therapeutic Type 2 inhibition in fibrotic diseases is of high interest. Furthermore, as demonstrated in cutaneous T cell lymphoma, advanced disease is characterized by Th1 to Th2 switch allowing cancer progression and immunosuppression. Development of targeted monoclonal antibodies against IL-4Rα (eg, dupilumab) led to a paradigm shift for the treatment of atopic dermatitis (AD) and stimulated research to better understand the role of Type 2 inflammation in other skin conditions. In this review, we summarize up to date knowledge on the role of Type 2 inflammation in skin diseases other than AD and highlight whether the use of Type 2 targeted therapies has been documented or is being investigated in clinical trials. This manuscript reviews the role of Type 2 inflammation in dermatitis, neurodermatitis, IgE-mediated dermatoses (eg, bullous pemphigoid, chronic spontaneous urticaria), sclerodermoid conditions and skin neoplasms.


Assuntos
Imunidade Inata , Imunoterapia/métodos , Dermatopatias/imunologia , Dermatopatias/terapia , Cicatrização/imunologia , Citocinas/imunologia , Humanos , Células Th2/imunologia
5.
Front Immunol ; 12: 751533, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858408

RESUMO

The gasdermin (GSDM) family, a novel group of structure-related proteins, consists of GSDMA, GSDMB, GSDMC, GSDMD, GSDME/DNFA5, and PVJK/GSDMF. GSDMs possess a C-terminal repressor domain, cytotoxic N-terminal domain, and flexible linker domain (except for GSDMF). The GSDM-NT domain can be cleaved and released to form large oligomeric pores in the membrane that facilitate pyroptosis. The emerging roles of GSDMs include the regulation of various physiological and pathological processes, such as cell differentiation, coagulation, inflammation, and tumorigenesis. Here, we introduce the basic structure, activation, and expression patterns of GSDMs, summarize their biological and pathological functions, and explore their regulatory mechanisms in health and disease. This review provides a reference for the development of GSDM-targeted drugs to treat various inflammatory and tissue damage-related conditions.


Assuntos
Proteínas de Neoplasias , Animais , Asma/genética , Asma/imunologia , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Perda Auditiva/genética , Perda Auditiva/imunologia , Humanos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , Proteínas de Neoplasias/fisiologia , Neoplasias/genética , Neoplasias/imunologia , Sepse/genética , Sepse/imunologia , Dermatopatias/genética , Dermatopatias/imunologia
6.
Nat Cell Biol ; 23(12): 1224-1239, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34876685

RESUMO

Defective silencing of retrotransposable elements has been linked to inflammageing, cancer and autoimmune diseases. However, the underlying mechanisms are only partially understood. Here we implicate the histone H3.3 chaperone Daxx, a retrotransposable element repressor inactivated in myeloid leukaemia and other neoplasms, in protection from inflammatory disease. Loss of Daxx alters the chromatin landscape, H3.3 distribution and histone marks of haematopoietic progenitors, leading to engagement of a Pu.1-dependent transcriptional programme for myelopoiesis at the expense of B-cell differentiation. This causes neutrophilia and inflammation, predisposing mice to develop an autoinflammatory skin disease. While these molecular and phenotypic perturbations are in part reverted in animals lacking both Pu.1 and Daxx, haematopoietic progenitors in these mice show unique chromatin and transcriptome alterations, suggesting an interaction between these two pathways. Overall, our findings implicate retrotransposable element silencing in haematopoiesis and suggest a cross-talk between the H3.3 loading machinery and the pioneer transcription factor Pu.1.


Assuntos
Cromatina/patologia , Proteínas Correpressoras/genética , Transtornos Leucocíticos/congênito , Chaperonas Moleculares/genética , Mielopoese/genética , Proteínas Proto-Oncogênicas/metabolismo , Transativadores/metabolismo , Animais , Doenças Autoimunes/genética , Doenças Autoimunes/patologia , Linfócitos B/citologia , Linhagem Celular , Cromatina/genética , Células-Tronco Hematopoéticas/citologia , Histonas/metabolismo , Humanos , Inflamação/patologia , Transtornos Leucocíticos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Retroelementos/genética , Dermatopatias/genética , Dermatopatias/imunologia , Dermatopatias/patologia
7.
Cells ; 10(12)2021 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-34943909

RESUMO

Systemic sclerosis (SSc) is a chronic connective tissue disorder characterized by immune dysregulation, chronic inflammation, vascular endothelial cell dysfunction, and progressive tissue fibrosis of the skin and internal organs. Moreover, increased cancer incidence and accelerated aging are also found. The increased cancer incidence is believed to be a result of chromosome instability. Accelerated cellular senescence has been confirmed by the shortening of telomere length due to increased DNA breakage, abnormal DNA repair response, and telomerase deficiency mediated by enhanced oxidative/nitrative stresses. The immune dysfunctions of SSc patients are manifested by excessive production of proinflammatory cytokines IL-1, IL-6, IL-17, IFN-α, and TNF-α, which can elicit potent tissue inflammation followed by tissue fibrosis. Furthermore, a number of autoantibodies including anti-topoisomerase 1 (anti-TOPO-1), anti-centromere (ACA or anti-CENP-B), anti-RNA polymerase enzyme (anti-RNAP III), anti-ribonuclear proteins (anti-U1, U2, and U11/U12 RNP), anti-nucleolar antigens (anti-Th/T0, anti-NOR90, anti-Ku, anti-RuvBL1/2, and anti-PM/Scl), and anti-telomere-associated proteins were also found. Based on these data, inflamm-aging caused by immune dysfunction-mediated inflammation exists in patients with SSc. Hence, increased cellular senescence is elicited by the interactions among excessive oxidative stress, pro-inflammatory cytokines, and autoantibodies. In the present review, we will discuss in detail the molecular basis of chromosome instability, increased oxidative stress, and functional adaptation by deranged immunome, which are related to inflamm-aging in patients with SSc.


Assuntos
Envelhecimento/genética , Fibrose/genética , Inflamação/genética , Escleroderma Sistêmico/genética , Envelhecimento/imunologia , Envelhecimento/patologia , Autoanticorpos/imunologia , Células Endoteliais/patologia , Fibrose/complicações , Fibrose/imunologia , Fibrose/patologia , Humanos , Doenças do Sistema Imunitário/complicações , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/patologia , Inflamação/complicações , Inflamação/imunologia , Inflamação/patologia , Mediadores da Inflamação , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Dermatopatias/complicações , Dermatopatias/genética , Dermatopatias/imunologia , Dermatopatias/patologia
8.
Clin Dermatol ; 39(6): 934-965, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34920833

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), is a single-stranded RNA virus whose sequence is known. COVID-19 is associated with a heterogeneous clinical phenotype ranging from asymptomatic to fatal disease. It appears that access to nasopharyngeal respiratory epithelia expressing angiotensin-converting enzyme (ACE) 2, the receptor for SARS-CoV-2, is followed by viral replication in the pulmonary alveolar septal capillary bed. We have demonstrated in earlier studies that incomplete viral particles, termed pseudovirions, dock to deep subcutaneous and other vascular beds, potentially contributing to the prothrombotic state and systemic complement activation that characterizes severe and critical COVID-19. A variety of skin eruptions have been described in the setting of SARS-CoV-2 infection and more recently, after COVID-19 vaccination. The vaccines deliver a laboratory-synthesized mRNA that encodes a protein that is identical to the spike glycoprotein of SARS-CoV-2, allowing the production of immunogenic spike glycoprotein that will then elicit T cell and B cell adaptive immune responses. In this contribution, we review an array of cutaneous manifestations of COVID-19 that provide an opportunity to study critical pathophysiologic mechanisms that underlie all clinical facets of COVID-19, ranging from asymptomatic/mild to severe and critical COVID-19. We classify cutaneous COVID-19 according to underlying pathophysiologic principles. In this regard we propose three main pathways: (1) complement mediated thrombotic vascular injury syndromes deploying the alternative and mannan binding lectin pathways and resulting in the elaboration of cytokines like interleukin 6 from endothelium in the setting of severe and critical COVID-19 and (2) the robust T cell and type I interferon-driven inflammatory and (3) humoral-driven immune complex mediated vasculitic cutaneous reactions observed with mild and moderate COVID-19. Presented are novel data on cutaneous vaccine reactions that manifest a clinical and morphologic parallel with similar eruptions observed in patients with mild and moderate COVID-19 and in some cases represent systemic eczematoid hypersensitivity reactions to a putative vaccine-based antigen versus unmasking subclinical hypersensitivity due to immune enhancing effects of the vaccine. Finally, we demonstrate for the first time the localization of human synthesized spike glycoprotein after the COVID-19 vaccine to the cutaneous and subcutaneous vasculature confirming the ability of SARS-CoV-2 spike glycoprotein to bind endothelium in the absence of intact virus.


Assuntos
COVID-19 , Dermatopatias/virologia , COVID-19/imunologia , COVID-19/fisiopatologia , Vacinas contra COVID-19 , Citocinas , Humanos , Dermatopatias/imunologia , Glicoproteína da Espícula de Coronavírus
9.
Dermatol Online J ; 27(9)2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34755974

RESUMO

Adults with chronic inflammatory skin disease are at increased risk of vaccine-preventable illnesses and infections, likely because of the underlying disease itself and also their treatment with immunosuppressive and immunomodulatory medications. Despite the association between these agents and increased susceptibility to infection, vaccination rates in dermatology patients remain low. Although preventative care such as vaccinations is typically managed by primary care providers, dermatologists serve a critical role in spreading awareness of the specific risks of immunosuppressive and immunomodulatory agents and promoting understanding of individualized vaccine recommendations. In this review, we provide evidence-based information on vaccine recommendations for adult dermatology patients, specific to age and medication use.


Assuntos
Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Dermatopatias/tratamento farmacológico , Dermatopatias/imunologia , Vacinação , Doença Crônica , Dermatologistas , Suscetibilidade a Doenças/imunologia , Humanos , Aceitação pelo Paciente de Cuidados de Saúde , Educação de Pacientes como Assunto , Papel do Médico , Fatores de Risco , Vacinação/efeitos adversos
10.
Int J Immunopathol Pharmacol ; 35: 20587384211042115, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34541915

RESUMO

BACKGROUND: Hypercoagulability is a risk factor of thromboembolic events in COVID-19. Anti-phospholipid (aPL) antibodies have been hypothesized to be involved. Typical COVID-19 dermatological manifestations of livedo reticularis and digital ischemia may resemble cutaneous manifestations of anti-phospholipid syndrome (APS). OBJECTIVES: To investigate the association between aPL antibodies and thromboembolic events, COVID-19 severity, mortality, and cutaneous manifestations in patients with COVID-19. METHODS: aPL antibodies [anti-beta2-glycoprotein-1 (B2GP1) and anti-cardiolipin (aCL) antibodies] were titered in frozen serum samples from hospitalized COVID-19 patients and the patients' clinical records were retrospectively analyzed. RESULTS: 173 patients were enrolled. aPL antibodies were detected in 34.7% of patients, anti-B2GP1 antibodies in 30.1%, and aCL antibodies in 10.4%. Double positivity was observed in 5.2% of patients. Thromboembolic events occurred in 9.8% of patients, including 11 pulmonary embolisms, 1 case of celiac tripod thrombosis, and six arterial ischemic events affecting the cerebral, celiac, splenic, or femoral-popliteal arteries or the aorta. aPL antibodies were found in 52.9% of patients with vascular events, but thromboembolic events were not correlated to aPL antibodies (adjusted OR = 1.69, p = 0.502). Ten patients (5.8%) had cutaneous signs of vasculopathy: nine livedo reticularis and one acrocyanosis. No significant association was observed between the presence of cutaneous vasculopathy and aPL antibodies (p = 0.692). CONCLUSIONS: Anti-phospholipid antibodies cannot be considered responsible for hypercoagulability and thrombotic events in COVID-19 patients. In COVID-19 patients, livedo reticularis and acrocyanosis do not appear to be cutaneous manifestations of APS.


Assuntos
Anticorpos Antifosfolipídeos/sangue , COVID-19/complicações , SARS-CoV-2 , Dermatopatias/sangue , Doenças Vasculares/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Anticardiolipina/sangue , COVID-19/sangue , COVID-19/imunologia , COVID-19/mortalidade , Feminino , Hospitalização , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos Soroepidemiológicos , Dermatopatias/imunologia , Dermatopatias/mortalidade , Doenças Vasculares/imunologia , Doenças Vasculares/mortalidade , beta 2-Glicoproteína I/imunologia
11.
Eur J Med Res ; 26(1): 110, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544497

RESUMO

BACKGROUND: Adult-onset Still's disease (AOSD) should be considered in the differential diagnosis of patients with endocarditis, with or without a cardiac decompensation. CASE PRESENTATION: We report the case of a 68-year-old Caucasian male diagnosed with AOSD after an initial acute manifestation of endocarditis with severe aortic acute manifestation of endocarditis with severe aortic insufficiency. The histological findings revealed Libman-Sacks endocarditis. He was treated with the IL-1 receptor inhibitor anakinra. Two years later the patient developed a symptomatic dilated cardiomyopathy with reduced ejection fraction (23.5%) and functional anti-beta-1-adrenergic receptor antibodies, which was initially treated with plasmapheresis; anakinra was maintained. While his AOSD symptoms responded well, our patient presented with recurrent arthritis in multiple joints, dual-energy CT showed urate deposition compatible with a gouty arthropathy. Over 7 years, he presented with recurrent episodes of arthritis and the adjustment of dosages of colchicine and febuxostat was needed. In 2018, our patient died due to a deterioration of his underlying cardiac disease. CONCLUSIONS: Only two cases with initial endocarditis prior to AOSD diagnosis have been published, and we are not aware of any other cases reporting -ß1AR-Ab development with DCM and gout in the setting of AOSD treated with anakinra.


Assuntos
Doenças Autoimunes/patologia , Inflamação/complicações , Dermatopatias/complicações , Doença de Still de Início Tardio/fisiopatologia , Idoso , Doenças Autoimunes/etiologia , Doenças Autoimunes/terapia , Humanos , Inflamação/imunologia , Inflamação/patologia , Masculino , Prognóstico , Dermatopatias/imunologia , Dermatopatias/patologia
12.
J Dermatol Sci ; 104(1): 2-10, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34493430

RESUMO

More than 100 years have passed since Elie Metchnikoff discovered macrophage. Over the recent decade, attracting information about macrophage polarization have been reported. This is because many molecules have been identified as markers of macrophage polarization. Additionally, mechanistic insights have been demonstrated by experiments with various stimuli-induced macrophage polarization. Historically and simply, macrophages are divided into M1 (classically activated) and M2 (alternatively activated). However, some of them are not specific yet. Studies in the field of cardiology revealed the plasticity of macrophages and their subsets are divided into details: Mhem, MHb, Mox and M4 macrophages. M2 macrophages were further divided in M2a, M2b, M2c and M2d. There appears to be more phenotypes of macrophages. However, there still lack studies in dermatological field. This review summarizes the spectrum of macrophage activation and finding about various roles of macrophages in the dermatological field.


Assuntos
Ativação de Macrófagos , Macrófagos/imunologia , Dermatopatias/imunologia , Pele/imunologia , Animais , Diferenciação Celular , Plasticidade Celular/imunologia , Humanos , Pele/citologia , Pele/patologia , Dermatopatias/patologia
16.
Int J Mol Sci ; 22(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445713

RESUMO

In health, the non-recirculating nature and long-term persistence of tissue-resident memory T cells (TRMs) in tissues protects against invading pathogens. In disease, pathogenic TRMs contribute to the recurring traits of many skin diseases. We aimed to conduct a systematic literature review on the current understanding of the role of TRMs in skin diseases and identify gaps as well as future research paths. EMBASE, PubMed, SCOPUS, Web of Science, Clinicaltrials.gov and WHO Trials Registry were searched systematically for relevant studies from their inception to October 2020. Included studies were reviewed independently by two authors. This study was conducted in accordance with the PRISMA-S guidelines. This protocol was registered with the PROSPERO database (ref: CRD42020206416). We identified 96 studies meeting the inclusion criteria. TRMs have mostly been investigated in murine skin and in relation to infectious skin diseases. Pathogenic TRMs have been characterized in various skin diseases including psoriasis, vitiligo and cutaneous T-cell lymphoma. Studies are needed to discover biomarkers that may delineate TRMs poised for pathogenic activity in skin diseases and establish to which extent TRMs are contingent on the local skin microenvironment. Additionally, future studies may investigate the effects of current treatments on the persistence of pathogenic TRMs in human skin.


Assuntos
Memória Imunológica/imunologia , Dermatopatias/imunologia , Linfócitos T/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Humanos , Linfoma Cutâneo de Células T/imunologia , Especificidade de Órgãos/imunologia , Psoríase/imunologia , Pele/metabolismo , Dermatopatias/fisiopatologia , Linfócitos T/imunologia , Vitiligo/imunologia
18.
Front Immunol ; 12: 674871, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290700

RESUMO

Rosacea is a common chronic inflammatory condition that mainly affects the central face. However, the molecular background of the normal central face and the transcriptional profiling and immune cell composition of rosacea lesions remain largely unknown. Here, we performed whole-skin and epidermal RNA-seq of central facial skin from healthy individuals, lesions and matched normal skin from rosacea patients. From whole-skin RNA-seq, the site-specific gene signatures for central facial skin were mainly enriched in epithelial cell differentiation, with upregulation of the activator protein-1 (AP1) transcription factor (TF). We identified the common upregulated inflammatory signatures and diminished keratinization signature for rosacea lesions. Gene ontology, pathway, TF enrichment and immunohistochemistry results suggested that STAT1 was the potential core of the critical TF networks connecting the epithelial-immune crosstalk in rosacea lesions. Epidermal RNA-seq and immunohistochemistry analysis further validated the epithelial-derived STAT1 signature in rosacea lesions. The epidermal STAT1/IRF1 signature was observed across ETR, PPR, and PhR subtypes. Immune cell composition revealed that macrophages were common in all 3 subtypes. Finally, we described subtype-specific gene signatures and immune cell composition correlated with phenotypes. These findings reveal the specific epithelial differentiation in normal central facial skin, and epithelial-immune crosstalk in lesions providing insight into an initial keratinocyte pattern in the pathogenesis of rosacea.


Assuntos
Rosácea/imunologia , Fator de Transcrição STAT1/metabolismo , Pele/patologia , Adulto , Feminino , Perfilação da Expressão Gênica , Humanos , Imunidade Inata , Queratinócitos/metabolismo , Pessoa de Meia-Idade , RNA-Seq , Rosácea/fisiopatologia , Dermatopatias/imunologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
19.
Am J Clin Dermatol ; 22(6): 837-851, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34287768

RESUMO

Topical corticosteroid phobia may lead to poor adherence, resulting in persistent disease and escalation to systemic agents. The aim of this paper was to review current literature to assess topical steroid phobia prevalence, populations most at risk, reasons behind steroid phobia, and interventions to reduce it. A systematic search of PubMed, Ovid (Journals@Ovid, MEDLINE), ScienceDirect, and Web of Science was performed. Studies ranged from May 2000 to February 2021. In total, 37 articles met the inclusion criteria. There was inter-study variation in the way steroid phobia is defined, from concern to irrational fear. The worldwide prevalence of topical steroid phobia ranges from 31 to 95.7% and does not differ with patient race/ethnicity or dermatological condition. Female patients and caregivers, and those who have experienced side effects of topical corticosteroids are most likely to express steroid phobia. Reasons for steroid phobia include lack of education, fear of side effects, polypharmacy, misinformation, negative experience with topical steroids, and frequently changing of clinics. Successful interventions to address steroid phobia include patient education in the form of educational videos followed by individualized oral education based on concerns, and demonstrations of application of topical steroids. Multiple interventions address topical corticosteroid phobia and improve adherence of topical corticosteroids in the management of dermatological conditions. Providers should screen patients for steroid phobia, especially in populations particularly at risk. Interventions using patient education should be individualized based on concerns expressed during screening. Further research should investigate if reducing steroid phobia can in fact improve long-term adherence.


Assuntos
Fármacos Dermatológicos/efeitos adversos , Glucocorticoides/efeitos adversos , Educação de Pacientes como Assunto/métodos , Transtornos Fóbicos/epidemiologia , Dermatopatias/tratamento farmacológico , Administração Cutânea , Fármacos Dermatológicos/administração & dosagem , Glucocorticoides/administração & dosagem , Humanos , Adesão à Medicação/psicologia , Transtornos Fóbicos/diagnóstico , Transtornos Fóbicos/etiologia , Transtornos Fóbicos/prevenção & controle , Prevalência , Fatores de Risco , Dermatopatias/imunologia
20.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209865

RESUMO

Saliva is easy to access, non-invasive and a useful source of information useful for the diagnosis of serval inflammatory and immune-mediated diseases. Following the advent of genomic technologies and -omic research, studies based on saliva testing have rapidly increased and human salivary proteome has been partially characterized. As a proteomic protocol to analyze the whole saliva proteome is not currently available, the most common aim of the proteomic analysis is to discriminate between physiological and pathological conditions. The salivary proteome has been initially investigated in several diseases: oral squamous cell carcinoma and oral leukoplakia, chronic graft-versus-host disease, and Sjögren's syndrome. Otherwise, salivary proteomics studies in the dermatological field are still in the initial phase, thus the aim of this review is to collect the best research evidence on the role of saliva proteomics analysis in immune-mediated skin diseases to understand the direction of research in this field. The results of PRISMA analysis reported herein suggest that human saliva analysis could provide significant data for the diagnosis and prognosis of several immune-mediated and inflammatory skin diseases in the next future.


Assuntos
Proteômica/métodos , Saliva/metabolismo , Dermatopatias/diagnóstico , Biomarcadores/metabolismo , Diagnóstico Precoce , Humanos , Prognóstico , Dermatopatias/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...