ALBERTO JOSE DA SILVA DUARTE

(Fonte: Lattes)
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Lattes
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Departamento de Patologia, Faculdade de Medicina - Docente
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina

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Autor: AOKI, Valeria ×

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Agora exibindo 1 - 10 de 21
  • article 11 Citação(ões) na Scopus
    Evidence of regulatory myeloid dendritic cells and circulating inflammatory epidermal dendritic cells-like modulated by Toll-like receptors 2 and 7/8 in adults with atopic dermatitis
    (2017) SANTOS, Vanessa G. dos; ORFALI, Raquel L.; TITZ, Tiago de Oliveira; DUARTE, Alberto J. da Silva; SATO, Maria N.; AOKI, Valeria
    Backgroud Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and xerosis. Dendritic cells (DC) play an essential role in tissue inflammation in atopic dermatitis (AD) skin, especially the inflammatory epidermal dendritic cells (IDEC), a particular subset of myeloid dendritic cells (mDC). The aim of the present study was to assess the phenotype and function of mDC and circulating IDEC-like in peripheral blood mononuclear cells (PBMC) of adults with AD. Methods We selected 21 AD patients and 21 non-AD controls, age and gender matched. Expressions of Fc epsilon RI, CD36, TNF, IFN-gamma , and IL-10 in mDC were analyzed by flow cytometry under various stimuli, such as staphylococcal enterotoxin B (SEB), TLR2 (Pam3CSK4), TLR4 (LPS), and TLR7/8 (CL097) agonists. Results The most prominent findings in AD patients were: (i) enhanced frequency of IL-10 under TLR4 (LPS), and decreased frequency of IFN-gamma and TNF under TLR2 (Pam3CSK4) and 7/8 (CL097) stimulation in classic mDC; (ii) elevation of circulating IDEC-like frequency with TLR2 (Pam3CSK4) stimuli, augmented frequency of IFN-gamma in nonstimulated condition, and of IL-10 under TLR7/8 (CL097) stimuli in IDEC-like population. Conclusions In AD individuals, classic mDC showed an immunomodulatory profile, favoring tolerance in a combined action with IDEC-like, and inducing Th1 polarization. Our findings indicate a potential role of IDEC-like in the maintenance of inflammation in atopic dermatitis patients; moreover, IDEC-like may exert a regulatory impact on T cells of AD individuals through IL-10, often induced by agonist mimicking single stranded RNA virus.
  • article 10 Citação(ões) na Scopus
    Activation of myeloid dendritic cells, effector cells and regulatory T cells in lichen planus
    (2016) DOMINGUES, Rosana; CARVALHO, Gabriel Costa de; AOKI, Valeria; DUARTE, Alberto Jose da Silva; SATO, Maria Notomi
    Background: Lichen planus (LP) is a chronic mucocutaneous inflammatory disease. Evaluating the balance between regulatory T cells and effector T cells could be useful for monitoring the proinflammatory profile of LP. Therefore, this study aimed to assess populations of dendritic cells (DCs) and regulatory and effector T cells in peripheral blood samples collected from patients with LP to evaluate the polyfunctionality of T cells upon toll-like receptor (TLR) activation. Methods: Peripheral blood mononuclear cells collected from 18 patients with LP and 22 healthy control subjects were stimulated with agonists of TLR4, TLR7, TLR7/TLR8 or TLR9. Frequencies of circulating IFN-alpha(+) plasmacytoid DCs (pDCs); TNF-alpha(+) myeloid DCs (mDCs); regulatory T cells (Tregs); and IL-17-, IL-10-, IL-22-, TNF-, and IFN-gamma-secreting T cells were assessed via flow cytometry. Results: The frequencies of regulatory CD4(+) and CD8(+)CD25(+)Foxp3(+)CD127(low/-)T cells and TNF-alpha(+) mDCs were induced following activation with TLR4, TLR7 and TLR8 agonists in the LP group. Moreover, increased baseline frequencies of CD4(+)IL-10(+) T cells and CD8(+)IL-22(+) or IFN-gamma(+) T cells were found. In the LP group, TLR4 activation induced an increased frequency of CD4(+) IFN-gamma(+) T cells, while TLR7/8 and staphylococcal enterotoxin B (SEB) activation induced an increased frequency of CD8(+)IL-22(+) T cells. An increased frequency of polyfunctional CD4(+) T cells that simultaneously secreted 3 of the evaluated cytokines (not including IL-10) was verified upon TLR7/8/9 activation, while polyfunctional CD8(+) T cells were already detectable at baseline. Conclusions: TLR-mediated activation of the innate immune response induced the production of proinflammatory mDCs, Tregs and polyfunctional T cells in patients with LP. Therefore, TLR activation has an adjuvant role in inducing both innate and adaptive immune responses.
  • article 8 Citação(ões) na Scopus
    IgG from Adult Atopic Dermatitis (AD) Patients Induces Nonatopic Neonatal Thymic Gamma-Delta T Cells (gamma delta T) to Acquire IL-22/IL-17 Secretion Profile with Skin-Homing Properties and Epigenetic Implications Mediated by miRNA
    (2022) FAGUNDES, Beatriz Oliveira; SOUSA, Thamires Rodrigues de; NASCIMENTO, Andrezza; FERNANDES, Lorena Abreu; SGNOTTO, Fabio da Ressureicao; ORFALI, Raquel Leao; AOKI, Valeria; DUARTE, Alberto Jose da Silva; SANABANI, Sabri Saeed; VICTOR, Jefferson Russo
    gamma delta T cells mature in the human thymus, and mainly produce IL-17A or IFN-gamma, but can also produce IL-22 and modulate a variety of immune responses. Here, we aimed to evaluate whether IgG from AD patients (AD IgG) can functionally modulate thymic nonatopic gamma delta T cells. Thymic tissues were obtained from 12 infants who had not had an atopic history. Thymocytes were cultured in mock condition, or in the presence of either AD IgG or therapeutic intravenous IgG (IVIg). Following these treatments, intracellular cytokine production, phenotype, and microRNA expression profiles were investigated. AD IgG could downregulate alpha 4 beta 7, upregulate CLA, and induce the production of IFN-gamma, IL-17, and IL-22 in gamma delta T cells. Although both AD IgG and IVIg could directly interact with gamma delta T cell membranes, AD IgG could reduce gamma delta T cell apoptosis. AD IgG could upregulate nine miRNAs compared to IVIg, and six when compared to the mock condition. In parallel, some miRNAs were downregulated. Target gene prediction and functional analysis indicated that some target genes were enriched in the negative regulation of cellular transcription. This study shows that AD IgG influences the production of IL-17 and IL-22 by intrathymic nonatopic gamma delta T cells, and demonstrates epigenetic implications mediated by miRNAs.
  • article 14 Citação(ões) na Scopus
    IgG from atopic dermatitis patients induces non-atopic infant thymic invariant natural killer T (iNKT) cells to produce IL-4, IL-17, and IL-10
    (2020) SANTOS, Ludimila S.; SGNOTTO, Fabio da Ressureicao; SOUSA, Thamires R.; ORFALI, Raquel L.; AOKI, Valeria; DUARTE, Alberto Jose da Silva; VICTOR, Jefferson R.
    Background Atopic dermatitis (AD) pathogenesis still needs to be elucidated, but invariant natural killer T (iNKT) cell involvement was already described by several groups. Our group has demonstrated that IgG antibodies purified from AD patients can modulate cytokine production by thymic T cells. Here we aimed to investigate if IgG from AD patients can modulate infant non-atopic thymic iNKT cells cytokine production in order to collaborate with the elucidation of AD development in infancy. Methods Thymic tissues were obtained from children from non-atopic mothers, and IgG was purified from AD patients diagnosed as moderate or severe and, as controls, from subjects clinically classified as non-atopic individuals. PBMCs from non-atopic individuals were also used in this study. Results Our results demonstrated that IgG from AD patients could induce non-atopic children thymic iNKT cells to produce higher levels of intracellular IL-4, IL-10, and IL-17 when compared to all control conditions. No effect was observed in non-atopic adults peripheral iNKT. We also observed that IgG from AD patients induces an increase in the expression of CD4 and Ror gamma t transcription factor in non-atopic children thymic iNKT cells compared to the condition of all controls. Conclusions These observations suggest that IgG from AD patients can induce a cytokine profile by thymic iNKT cells from non-atopic infants compatible with the observations in AD development, which can collaborate with the elucidation of AD pathogenesis.
  • article 18 Citação(ões) na Scopus
    Staphylococcal enterotoxins modulate the effector CD4(+)T cell response by reshaping the gene expression profile in adults with atopic dermatitis
    (2019) ORFALI, Raquel Leao; YOSHIKAWA, Fabio Seiti Yamada; OLIVEIRA, Luanda Mara da Silva; PEREIRA, Natalli Zanete; LIMA, Josenilson Feitosa de; RAMOS, Yasmim Alefe Leuzzi; DUARTE, Alberto Jose da Silva; SATO, Maria Notomi; AOKI, Valeria
    Staphylococcus aureus colonizes the skin of atopic dermatitis (AD) individuals, but the impact of its enterotoxins on the chronic activation of CD4(+)T cells demands further analysis. We aimed to analyze the CD4(+)T cell anergy profile and their phenotypic and functional features through differential expression of cellular activation markers, cytokine production and response to staphylococcal enterotoxin A (SEA). A panel of 84 genes relevant to T cell anergy was assessed by PCR array in FACS-sorted CD4(+)T cells, and the most prominent genes were validated by RT-qPCR. We evaluated frequencies of circulating CD4(+)T cells secreting single or multiple (polyfunctional) cytokines (IL-17A, IL-22, TNF, IFN-gamma, and MIP-1 beta) and expression of activation marker CD38 in response to SEA stimulation by flow cytometry. Our main findings indicated upregulation of anergy-related genes (EGR2 and IL13) promoted by SEA in AD patients, associated to a compromised polyfunctional response particularly in CD4(+)CD38(+)T cells in response to antigen stimulation. The pathogenic role of staphylococcal enterotoxins in adult AD can be explained by their ability to downmodulate the activated effector T cell response, altering gene expression profile such as EGR2 induction, and may contribute to negative regulation of polyfunctional CD4(+)T cells in these patients.
  • article 8 Citação(ões) na Scopus
    Generation of Cytotoxic T Cells and Dysfunctional CD8 T Cells in Severe COVID-19 Patients
    (2022) GOZZI-SILVA, Sarah Cristina; OLIVEIRA, Luana de Mendonca; ALBERCA, Ricardo Wesley; PEREIRA, Natalli Zanete; YOSHIKAWA, Fabio Seiti; PIETROBON, Anna Julia; YENDO, Tatiana Mina; ANDRADE, Milena Mary de Souza; RAMOS, Yasmim Alefe Leuzzi; BRITO, Cyro Alves; OLIVEIRA, Emily Araujo; BESERRA, Danielle Rosa; ORFALI, Raquel Leao; AOKI, Valeria; DUARTE, Alberto Jose da Silva; SATO, Maria Notomi
    COVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The viral infection can evolve asymptomatically or can generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia based on the severity of symptoms in patients affected with COVID-19 is frequent. However, the profiles of CD4+ and CD8+ T cells regarding cytotoxicity and antiviral factor expression have not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study was to evaluate the phenotypic and functional profile of T lymphocytes in patients with moderate and severe/critical COVID-19. During the pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Notwithstanding lymphopenia, we observed an increase in the expression of CD28, a co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T lymphocytes as well as an increase in the frequency of CD4+ T cells, CD8+ T cells, and NK cells that express the immunological checkpoint protein PD-1 in patients with a severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T cells was already observed at the baseline level and scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T lymphocytes decreased the cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed by t-SNE, there were CD4+ T-cytotoxic and CD8+ T with low granzyme production, evidencing their dysfunction in severe/critical conditions. In addition, purified CD8+ T lymphocytes from patients with severe COVID-19 showed increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and, curiously, had reduced expression of TNF-alpha. The cytotoxic profile of CD4+ T cells may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T cells and CD8+ T cells in the severity of acute COVID-19 infection.
  • article 7 Citação(ões) na Scopus
    Impact of Inflammatory Immune Dysfunction in Psoriasis Patients at Risk for COVID-19
    (2021) YENDO, Tatiana Mina; SATO, Maria Notomi; BRANCO, Anna Claudia Calvielli Castelo; PIETROBON, Anna Julia; TEIXEIRA, Franciane Mouradian Emidio; RAMOS, Yasmim alefe Leuzzi; ALBERCA, Ricardo Wesley; VALENCIO, Cesar Giudice; ARRUDA, Vivian Nunes; ROMITI, Ricardo; ARNONE, Marcelo; HIRAYAMA, Andre Luis da Silva; DUARTE, Alberto Jose da Silva; AOKI, Valeria; ORFALI, Raquel Leao
    Psoriasis is an immune-mediated dermatosis usually associated with comorbidities. Treatment varies from topicals to systemic drugs and data on susceptibility to viral infections in psoriatic patients are scarce. The objectives of this study were to analyze psoriatic patients on different therapies who were at risk for COVID-19 for seroprevalence of SARS-COV-2, pro-inflammatory cytokine profile, comorbidities and outcomes in order to unveil the immunological mechanisms involved in the anti-viral response in patients with psoriasis. Seventy-five patients with psoriasis were divided according to treatment: immunobiologics, methotrexate, topicals and acitretin. Twenty healthy controls were included. Plasma samples were collected for: IgG SARS-COV-2 (ELISA); IL-27, IL-29 and IL-18 (ELISA); and IL-1 beta, IL-17A, IL-6 and TNF (cytometric array). Seropositivity for SARS-COV-2 was detected in 24 out of 75 psoriasis patients and did not relate to COVID-19 symptoms and/or hospitalization, despite associated comorbidities. Psoriasis patients who were asymptomatic for SARS-COV-2 exhibited immune imbalance with high levels of IL-18, IL-17A and IL-6, and low levels of IL-27 compared to healthy controls. Psoriasis groups showed significant increased cytokine levels only in the group with immunobiologics. Despite immune deviations and lower IL-27, which has a potential antiviral impact, psoriatic patients did not exhibit complications related to COVID-19. An understanding of this kind of proinflammatory profile of psoriatic patients and of the lack of severe outcomes for COVID-19 is essential to establish novel therapeutic approaches and preventive measures, including with regard to the concomitance of viral infections.
  • article 2 Citação(ões) na Scopus
    Platelet-Based Biomarkers for Diagnosis and Prognosis in COVID-19 Patients
    (2021) ALBERCA, Ricardo Wesley; SOLIS-CASTRO, Rosa Liliana; SOLIS-CASTRO, Maria Edith; CARDOSO, Fernanda; DUARTE, Alberto Jose da Silva; OLIVEIRA, Luana de Mendonca; PEREIRA, Natalli Zanete; GOZZI-SILVA, Sarah Cristina; OLIVEIRA, Emily Araujo de; AOKI, Valeria; ORFALI, Raquel Leao; BESERRA, Danielle Rosa; ANDRADE, Milena Mary de Souza; SATO, Maria Notomi
    Coronavirus disease 2019 (COVID-19) caused millions of deaths worldwide. COVID-19's clinical manifestations range from no symptoms to a severe acute respiratory syndrome, which can result in multiple organ failure, sepsis, and death. Severe COVID-19 patients develop pulmonary and extrapulmonary infections, with a hypercoagulable state. Several inflammatory or coagulatory biomarkers are currently used with predictive values for COVID-19 severity and prognosis. In this manuscript, we investigate if a combination of coagulatory and inflammatory biomarkers could provide a better biomarker with predictive value for COVID-19 patients, being able to distinguish between patients that would develop a moderate or severe COVID-19 and predict the disease outcome. We investigated 306 patients with COVID-19, confirmed by severe acute respiratory syndrome coronavirus 2 RNA detected in the nasopharyngeal swab, and retrospectively analyzed the laboratory data from the first day of hospitalization. In our cohort, biomarkers such as neutrophil count and neutrophil-to-lymphocyte ratio from the day of hospitalization could predict if the patient would need to be transferred to the intensive care unit but failed to identify the patients & PRIME; outcomes. The ratio between platelets and inflammatory markers such as creatinine, C-reactive protein, and urea levels is associated with patient outcomes. Finally, the platelet/neutrophil-to-lymphocyte ratio on the first day of hospitalization can be used with predictive value as a novel severity and lethality biomarker in COVID-19. These new biomarkers with predictive value could be used routinely to stratify the risk in COVID-19 patients since the first day of hospitalization.
  • article 9 Citação(ões) na Scopus
    Clinical Characteristics and Survival Analysis in Frequent Alcohol Consumers With COVID-19
    (2021) ALBERCA, Ricardo Wesley; RIGATO, Paula Ordonhez; RAMOS, Yasmim Alefe Leuzzi; TEIXEIRA, Franciane Mouradian Emidio; BRANCO, Anna Claudia Calvielli; FERNANDES, Iara Grigoletto; PIETROBON, Anna Julia; DUARTE, Alberto Jose da Silva; AOKI, Valeria; ORFALI, Raquel Leao; SATO, Maria Notomi
    Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can generate a systemic disease named coronavirus disease-2019 (COVID-19). Currently, the COVID-19 pandemic has killed millions worldwide, presenting huge health and economic challenges worldwide. Several risk factors, such as age, co-infections, metabolic syndrome, and smoking have been associated with poor disease progression and outcomes. Alcohol drinking is a common social practice among adults, but frequent and/or excessive consumption can mitigate the anti-viral and anti-bacterial immune responses. Therefore, we investigated if patients with self-reported daily alcohol consumption (DAC) presented alteration in the immune response to SARS-CoV-2. We investigated 122 patients with COVID-19 (101 male and 46 females), in which 23 were patients with DAC (18 men and 5 women) and 99 were non-DAC patients (58 men and 41 women), without other infections, neoplasia, or immunodeficiencies. Although with no difference in age, patients with DAC presented an increase in severity-associated COVID-19 markers such as C-reactive protein (CRP), neutrophil count, and neutrophil-to-lymphocyte ratio. In addition, patients with DAC presented a reduction in the lymphocytes and monocytes counts. Importantly, the DAC group presented an increase in death rate in comparison with the non-DAC group. Our results demonstrated that, in our cohort, DAC enhanced COVID-19-associated inflammation, and increased the number of deaths due to COVID-19.
  • article 13 Citação(ões) na Scopus
    Resveratrol Downmodulates Neutrophil Extracellular Trap (NET) Generation by Neutrophils in Patients with Severe COVID-19
    (2022) ANDRADE, Milena M. de Souza; LEAL, Vinicius N. C.; FERNANDES, Iara G.; GOZZI-SILVA, Sarah C.; BESERRA, Danielle R.; OLIVEIRA, Emily A.; TEIXEIRA, Franciane M. E.; YENDO, Tatiana M.; SOUSA, Maria da Gloria T.; TEODORO, Walcy R.; OLIVEIRA, Luana de M.; ALBERCA, Ricardo W.; AOKI, Valeria; DUARTE, Alberto J. S.; SATO, Maria N.
    The formation of microthrombi in lung autopsies indicates the involvement of NETs in the immunopathogenesis of severe COVID-19. Therefore, supplements inhibiting NET formation, in association with drugs with fewer adverse effects, should be a relevant strategy to attenuate the disease. Resveratrol (RESV) is a natural polyphenol with an important antiviral and antioxidant role. To modulate neutrophils from patients infected with SARS-CoV-2, we evaluated the in vitro effect of RESV on NET formation. Herein, we investigated 190 patients hospitalized with moderate, severe, and critical symptoms at Hospital das Clinicas, Brazil. We observed that neutrophilia in patients with severe COVID-19 infection is composed of neutrophils with activated profile able to release NET spontaneously. Notably, RESV decreased the neutrophil-activated status and the release of free DNA, inhibiting NET formation even under the specific PMA stimulus. At present, there is no evidence of the role of RESV in neutrophils from patients with COVID-19 infection. These findings suggest that adjunctive therapies with RESV may help decrease the inflammation of viral or bacterial infection, improving patient outcomes.