RAQUEL LEAO ORFALI
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
31 resultados
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- 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, ValeriaBackgroud 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.
- Increased expression of Filaggrin and Claudin-1 in the ocular surface of patients with atopic dermatitis(2022) CALLOU, T. M. P.; ORFALI, R. L.; SOTTO, M. N.; V, N. Pereira; ZANIBONI, M. C.; AOKI, V; BRITO, M. P.; MATSUDA, M.; SANTO, R. M.Background Atopic dermatitis (AD) is an itchy, chronic and inflammatory skin condition, with dysfunctional immune response and skin barrier defects. Reduction of filaggrin (FLG) and tight junctions (TJ) proteins, such as claudin-1 (CLDN-1), expression in cutaneous epithelial barrier is remarkable in AD pathogenesis. Ocular involvement occurs in approximately 40% of AD patients leading to changes in the structure of the conjunctiva. Objectives We aimed to evaluate the expression of FLG and CLDN-1 in the ocular surface of adults with AD, analysing bulbar conjunctival cells collected by a novel non-invasive cellular imprint. Methods Bulbar conjunctival epithelial cells were collected by cellular imprint technique, and FLG and CLDN-1 expression were assessed by immunofluorescence (IF) and real-time polymerase chain reaction (RT-PCR). Results We detected increased expression of FLG and CLDN-1, as well as their transcript levels in AD patients compared with healthy controls (HC). There was a positive correlation between tear film break-up time (TBUT) and FLG expression. Fluorescein staining was inversely associated with FLG expression. Conclusions Our results may reflect a reactive response of the ocular surface to AD-related ocular inflammation and associated dry eye disease. Further investigations focusing on the role of FLG and TJ expression in the ocular surface of AD patients may increment the understanding of the pathophysiology of extracutaneous AD and developing future targeted therapies.
- 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.
conferenceObject A 25-year overview of the atopic dermatitis outpatient clinic at the University of Sao Paulo Medical School, Brazil(2014) ZANIBONI, M. C.; ORFALI, R. L.; TAKAOKA, R.; ISHIZAKI, A. S.; AOKI, V.conferenceObject IgG from atopic dermatitis patients induces IL-17 and IL-10 production in infant intra-thymic TCD4 and TCD8 cells(2018) SGNOTTO, F. R.; OLIVEIRA, M. G.; LIRA, A. A. L.; INOUE, A. H. S.; TITZ, T. O.; ORFALI, R. L.; BENTO-DE-SOUZA, L.; SATO, M. N.; AOKI, V.; DUARTE, A. J. S.; VICTOR, J. R.conferenceObject Atopic dermatitis in adults: Augmented circulating IgG4 and IgE antibodies against Staphylococcus aureus enterotoxin B(2013) ORFALI, R. L.; SATO, M. N.; SANTOS, V. G. Dos; TITZ, T. O.; DUARTE, A. S.; TAKAOKA, R.; AOKI, V.The aim of this study was to evaluate the profile of anti-Staphylococcus aureus enterotoxin B (SEB) antibody (Ab) response in adults with AD. We selected 38 patients diagnosed as AD (Hanifin & Rajka's criteria), aged between 18 and 65, and 26 healthy controls (HC), aged between 20 and 47 years. Severity of the disease was established according to EASI (Eczema Area and Severity Index) and patients were graded as mild (28%), moderate (58%) and severe (14%). Sera were assessed for IgG subclasses, IgA, IgM and IgE against SEB by ELISA. The humoral response in AD patients to SEB showed elevated circulating IgE and IgG4 levels (p < 0.05 and p δ 0.001, respectively), and decreased IgA and IgM levels (p < 0.05). Severity of atopic dermatitis was related with low IgG1 and IgG3 levels (p < 0.05), and high IgE antibody response (p < 0.05) to SEB. Interestingly, absence of IgE and IgG1 response to SEB was seen in some AD patients (26.3% and 18.4% respectively). In AD, the immunoglobulin-related subtype Th2 lymphocytes, such as IgE and IgG4, appear to be relevant in the response to superantigens. These results emphasize an altered pattern of Ab response to SEB in AD, which is impaired according the disease severity.- Evaluating chronic pruritus prevalence, characteristics and effects on atopic dermatitis patients from a referral university hospital in Sao Paulo, Brazil: a cross-sectional study(2023) SOARES, Georgia Biazus; ORFALI, Raquel Leao; AVERBACH, Beatriz Lacerda; YOSIPOVITCH, Gil; AOKI, Valeria
bookPart Micoses superficiais(2019) ORFALI, Raquel Leão; TAKATU, Caroline Maris; ZANIBONI, Mariana ColombiniconferenceObject Staphylococcus aureus enterotoxins modulate IL-22-secreting cells in adults with atopic dermatitis(2018) ORFALI, R. L.; OLIVEIRA, L. M. S.; LIMA, J. F.; CARVALHO, G. C.; RAMOS, Y. A. L.; PEREIRA, N. Z.; VIEIRA, N. P.; ZANIBONI, M. C.; SATO, M. N.; AOKI, V.conferenceObject Impact of climate change on atopic dermatitis: A systematic search and review by the International Eczema Council(2023) WANG, S.; STEFANOVIC, N.; ORFALI, R. L.; AOKI, V.; BROWN, S.; DHAR, S.; EICHENFIELD, L. F.; FLOHR, C.; HA, A.; MORA, C.; MURASE, J.; ROSENBACH, M.; THYSSEN, J.; WEI, M. L.; IRVINE, A. D.; ABUABARA, K.