MARIA NOTOMI SATO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Dermatologia, Faculdade de Medicina - Docente
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina - Líder
12 resultados
Resultados de Busca
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- Low CCL2 and CXCL8 Production and High Prevalence of Allergies in Children with Microcephaly Due to Congenital Zika Syndrome(2023) BEZERRA, Wallace Pitanga; SALMERON, Amanda Costa Ayres; BRANCO, Anna Claudia Calvielli Castelo; MORAIS, Ingryd Camara; SALES, Valeria Soraya de Farias; MACHADO, Paula Renata Lima; SOUTO, Janeusa Trindade; ARAUJO, Joselio Maria Galvao de; GUEDES, Paulo Marcos da Matta; SATO, Maria Notomi; NASCIMENTO, Manuela Sales LimaCongenital Zika Syndrome (CZS) is associated with an increased risk of microcephaly in affected children. This study investigated the peripheral dysregulation of immune mediators in children with microcephaly due to CZS. Gene expression quantified by qPCR in whole blood samples showed an increase in IFN gamma and IL-13 transcripts in children affected with microcephaly compared to the control group. The microcephaly group exhibited significantly decreased CCL2 and CXCL8 levels in serum, quantified by CBA assay. An allergic profile questionnaire revealed a high prevalence of allergies in the microcephaly group. In accordance, elevated serum IgE level measured by the Proquantum Immunoassay was observed in children affected with microcephaly compared to the control group. Altogether, these findings show a persistent systemic inflammation in children with microcephaly due to CZS and suggest a possible impairment in leukocyte migration caused by low production of CCL2 and CXCL8, in addition to high levels of IgE associated with high prevalence of allergies. The dysregulation of inflammatory genes and chemokines underscores the importance of understanding the immunological characteristics of CZS. Further investigation into the long-term consequences of systemic inflammation in these children is crucial for developing appropriate therapeutic strategies and tailored vaccination protocols.
- Outlining the skin-homing and circulating CLA+NK cells in patients with severe atopic dermatitis(2024) LIMA, Josenilson Feitosa de; TEIXEIRA, Franciane Mouradian Emidio; RAMOS, Yasmim alefe Leuzzi; CARVALHO, Gabriel Costa de; BRANCO, Anna Claudia Calvielli Castelo; PEREIRA, Naiura Vieira; SOTTO, Mirian Nacagami; AOKI, Valeria; SATO, Maria Notomi; ORFALI, Raquel LeaoAtopic dermatitis (AD) is a complex, multifactorial skin disease, characterized by pruritus and predominant Th2 inflammation. Innate immune cells may play a role in AD development and are composed of granulocytes, macrophages, innate-like T cells, and innate lymphoid cells. This study investigates the phenotypic and functional profile of circulating CLA(+) natural killer (NK) cells and its role in the skin-homing to NK cells infiltrated in adults' skin with AD. We selected 44 AD patients and 27 non-AD volunteers for the study. The results showed increased frequencies of both CLA(+)CD56(bright) and CLA(+)CD56(dim) NK cell populations in the peripheral blood, mainly in severe AD patients. Upon SEB stimulation, we observed an augmented percentage of CLA(+)CD56(dim) NK cells expressing CD107a, IFN-gamma, IL-10, and TNF, reinforcing the role of staphylococcal enterotoxins in AD pathogenesis. Additionally, we demonstrated increased dermal expression of both NK cell markers NCAM-1/CD56 and pan-granzyme, corroborating the skin-homing, mostly in severe AD. Further studies are necessary to elucidate the potential role of NK cells in the chronification of the inflammatory process in AD skin, as well as their possible relationship with staphylococcal enterotoxins, and as practicable therapeutic targets.
- Enhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvants(2024) TEIXEIRA, Franciane Mouradian Emidio; OLIVEIRA, Luana de Mendonca; BRANCO, Anna Claudia Calvielli Castelo; ALBERCA, Ricardo Wesley; SOUSA, Emanuella Sarmento Alho de; LEITE, Bruno Henrique de Sousa; ADAN, Wenny Camilla dos Santos; DUARTE, Alberto Jose da Silva; LINS, Roberto Dias; SATO, Maria Notomi; VIANA, Isabelle Freire TabosaZika virus (ZIKV) is a re-emerging pathogen with high morbidity associated to congenital infection. Despite the scientific advances since the last outbreak in the Americas, there are no approved specific treatment or vaccines. As the development of an effective prophylactic approach remains unaddressed, DNA vaccines surge as a powerful and attractive candidate due to the efficacy of sequence optimization in achieving strong immune response. In this study, we developed four DNA vaccine constructs encoding the ZIKV prM/M (pre-membrane/membrane) and E (envelope) proteins in conjunction with molecular adjuvants. The DNA vaccine candidate (called ZK_Delta STP), where the entire membrane-anchoring regions were completely removed, was far more immunogenic compared to their counterparts. Furthermore, inclusion of the tPA-SP leader sequence led to high expression and secretion of the target vaccine antigens, therefore contributing to adequate B cell stimulation. The ZK_Delta STP vaccine induced high cellular and humoral response in C57BL/6 adult mice, which included high neutralizing antibody titers and the generation of germinal center B cells. Administration of ZK-Delta STP incorporating aluminum hydroxide (Alum) adjuvant led to sustained neutralizing response. In consistency with the high and long-term protective response, ZK_Delta STP+Alum protected adult mice upon viral challenge. Collectively, the ZK_Delta STP+Alum vaccine formulation advances the understanding of the requirements for a successful and protective vaccine against flaviviruses and is worthy of further translational studies.
- Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression(2024) SAMORANO, Luciana Paula; MANFRERE, Kelly Cristina Gomes; PEREIRA, Naiura Vieira; TAKAOKA, Roberto; VALENTE, Neusa Yuriko Sakai; SOTTO, Mirian Nacagami; SILVA, Luiz Fernando Ferraz; SATO, Maria Notomi; AOKI, ValeriaBackground: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). Objective: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. Methods: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-alpha, IFN-gamma, TARC, and CCL-22. Results: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. Study limitations: Small sample size and limited length of follow-up. Conclusions: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA. (c) 2023 Published by Elsevier Espana, S.L.U. on behalf of Sociedade Brasileira de Dermatologia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
- Severe COVID-19 patients show a dysregulation of the NLRP3 inflammasome in circulating neutrophils(2023) LEAL, Vinicius N. C.; ANDRADE, Milena M. S.; TEIXEIRA, Franciane M. E.; CAMBUI, Raylane A. G.; ROA, Mariela E. G. V.; MARRA, Leticia G.; YAMADA, Suemy M.; ALBERCA, Ricardo W.; GOZZI-SILVA, Sarah C.; YENDO, Tatiana M.; NETTO, Lucas C.; DUARTE, Alberto J. S.; SATO, Maria N.; PONTILLO, AlessandraSARS-CoV-2 triggers inflammasome-dependent release of pro-inflammatory cytokine IL-1 beta and pyroptosis, therefore, contributes to the huge inflammatory response observed in severe COVID-19 patients. Less is known about the engagement of inflammasome in neutrophils, main players in tissue injury and severe infection. We studied the activation of the inflammasome in neutrophils from severe COVID-19 patients and assessed its consequence in term of cells contribution to disease pathogenesis. We demonstrated that NLRP3 inflammasome is dramatically activated in neutrophils from severe COVID-19 patients and that the specific inhibition of NLRP3 reverts neutrophils' activation. Next, the stimulation of severe patients' neutrophils with common NLRP3 stimuli was not able to further activate the inflammasome, possibly due to exhaustion or increased percentage of circulating immature neutrophils. Collectively, our results demonstrate that the NLRP3 inflammasome is hyperactivated in severe COVID-19 neutrophils and its exhaustion may be responsible for the increased susceptibility to subsequent (and possibly lethal) infections. Our findings thus include a novel piece in the complex puzzle of COVID-19 pathogenesis.
- Immunological evaluation of young unvaccinated patients with Turner syndrome after COVID-19(2023) CASTRO, Mateus V. de; SILVA, Monize V. R.; OLIVEIRA, Luana de M.; GOZZI-SILVA, Sarah C.; NASLAVSKY, Michel S.; SCLIAR, Marilia O.; MAGALHAES, Monize L.; ROCHA, Katia M. da; NUNES, Kelly; CASTELLI, Erick C.; MAGAWA, Jhosiene Y.; SANTOS, Keity S.; CUNHA-NETO, Edecio; SATO, Maria N.; ZATZ, MayanaObjectives: The X-chromosome contains the largest number of immune-related genes, which play a major role in COVID-19 symptomatology and susceptibility. Here, we had a unique opportunity to investigate, for the first time, COVID-19 outcomes in six unvaccinated young Brazilian patients with Turner syndrome (TS; 45, X0), including one case of critical illness in a child aged 10 years, to evaluate their immune response according to their genetic profile. Methods: A serological analysis of humoral immune response against SARS-CoV-2, phenotypic character-ization of antiviral responses in peripheral blood mononuclear cells after stimuli, and the production of cytotoxic cytokines of T lymphocytes and natural killer cells were performed in blood samples collected from the patients with TS during the convalescence period. Whole exome sequencing was also performed.Results: Our volunteers with TS showed a delayed or insufficient humoral immune response to SARS-CoV-2 (particularly immunoglobulin G) and a decrease in interferon-gamma production by cluster of differentiation (CD)4 + and CD8 + T lymphocytes after stimulation with toll-like receptors 7/8 agonists. In contrast, we observed a higher cytotoxic activity in the volunteers with TS than the volunteers without TS after phor-bol myristate acetate/ionomycin stimulation, particularly granzyme B and perforin by CD8 + and natural killer cells. Interestingly, two volunteers with TS carry rare genetic variants in genes that regulate type I and III interferon immunity.Conclusion: Following previous reports in the literature for other conditions, our data showed that pa-tients with TS may have an impaired immune response against SARS-CoV-2. Furthermore, other medical conditions associated with TS could make them more vulnerable to COVID-19.(c) 2023 The Author(s).
- Upregulation of PD-1 Expression and High sPD-L1 Levels Associated with COVID-19 Severity(2022) BESERRA, Danielle Rosa; ALBERCA, Ricardo Wesley; BRANCO, Anna Claudia Calvielli Castelo; OLIVEIRA, Luana de Mendonca; ANDRADE, Milena Mary de Souza; GOZZI-SILVA, Sarah Cristina; TEIXEIRA, Franciane Mouradian Emidio; YENDO, Tatiana Mina; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCOVID-19 has several mechanisms that can lead to lymphocyte depletion/exhaustion. The checkpoint inhibitor molecule programmed death protein 1 (PD-1) and its programmed death-ligand 1 (PDL-1) play an important role in inhibiting cellular activity as well as the depletion of these cells. In this study, we evaluated PD-1 expression in TCD4+, TCD8+, and CD19+ lymphocytes from SARS-CoV-2-infected patients. A decreased frequency of total lymphocytes and an increased PD-1 expression in TCD4+ and CD19+ lymphocytes were verified in severe/critical COVID-19 patients. In addition, we found a decreased frequency of total monocytes with an increased PD-1 expression on CD14+ monocytes in severe/critical patients in association with the time of infection. Moreover, we observed an increase in sPD-L1 circulant levels associated with the severity of the disease. Overall, these data indicate an important role of the PD-1/PDL-1 axis in COVID-19 and may provide a severity-associated biomarker and therapeutic target during SARS-CoV-2 infection.
- A common variant close to the ""tripwire"" linker region of NLRP1 contributes to severe COVID-19(2023) LEAL, Vinicius N. C.; PAULINO, Leandro M.; CAMBUI, Raylane A. G.; ZUPELLI, Thiago G.; YAMADA, Suemy M.; OLIVEIRA, Leonardo A. T.; DUTRA, Valeria de F.; BUB, Carolina B.; SAKASHITA, Araci M.; YOKOYAMA, Ana Paula H.; KUTNER, Jose M.; VIEIRA, Camila A.; SANTIAGO, Wellyngton M. de S.; ANDRADE, Milena M. S.; TEIXEIRA, Franciane M. E.; ALBERCA, Ricardo W.; GOZZI-SILVA, Sarah C.; YENDO, Tatiana M.; NETTO, Lucas C.; DUARTE, Alberto J. S.; SATO, Maria N.; VENTURINI, James; PONTILLO, AlessandraObjective and design The heterogeneity of response to SARS-CoV-2 infection is directly linked to the individual genetic background. Genetic variants of inflammasome-related genes have been pointed as risk factors for several inflammatory sterile and infectious disease. In the group of inflammasome receptors, NLRP1 stands out as a good novel candidate as severity factor for COVID-19 disease. Methods To address this question, we performed an association study of NLRP1, DPP9, CARD8, IL1B, and IL18 single nucleotide variants (SNVs) in a cohort of 945 COVID-19 patients. Results The NLRP1 p.Leu155His in the linker region, target of viral protease, was significantly associated to COVID-19 severity, which could contribute to the excessive cytokine release reported in severe cases. Conclusion Inflammasome genetic background contributes to individual response to SARS-CoV-2.
- IgG from patients with mild or severe COVID-19 reduces the frequency and modulates the function of peripheral mucosal-associated invariant T cells in PBMCs from healthy individuals(2023) MACHADO, Nicolle Rakanidis; FAGUNDES, Beatriz Oliveira; FERNANDES, Iara Grigoletto; RECHE, Daniela Terra De Apoena; SATO, Maria Notomi; VICTOR, Jefferson RussoLower levels of peripheral mucosal-associated invariant T (MAIT) cells have been observed in the peripheral blood of patients with severe coronavirus disease 2019 (COVID-19). Following on from previous research into the effect of the IgG repertoire on human lymphocytes, the present study aimed to evaluate if immunoglobulin G (IgG) antibodies obtained from patients with mild or severe COVID-19 contribute to these effects on MAIT cells. Culture experiments were performed using healthy human peripheral blood mononuclear cells (PBMCs) and different repertoires of IgG obtained from patients with COVID-19 as a mild or severe disease and compared with mock, healthy control or therapeutic IgG conditions. The results indicate that the IgG repertoire induced during the development of mild and severe COVID-19 has, per se, the in vitro potential to reduce the frequency of MAIT cells and the production of IFN-gamma by the MAIT cell population in PBMCs from healthy individuals. In conclusion, the results of the present study indicate that IgG in patients with severe COVID-19 may participate in the reduction of peripheral MAIT cell frequency and hinder the antiviral activity of these cells.
- Imbalanced IL-1B and IL-18 Expression in Sezary Syndrome(2023) MANFRERE, Kelly Cristina Gomes; TORREALBA, Marina Passos; FERREIRA, Frederico Moraes; SOUSA, Emanuella Sarmento Alho de; MIYASHIRO, Denis; TEIXEIRA, Franciane Mouradian Emidio; CUSTODIO, Ricardo Wesley Alberca; NAKAYA, Helder I.; RAMOS, Yasmin Alefe Leuzzi; SOTTO, Mirian Nacagami; WOETMANN, Anders; ODUM, Niels; DUARTE, Alberto Jose da Silva; SANCHES, Jose Antonio; SATO, Maria NotomiSezary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18, as key signaling molecules in the immune system, are produced in an inactive form and cleave to the active form by inflammasomes. In this study, we assessed the skin, serum, peripheral mononuclear blood cell (PBMC) and lymph-node samples of SS patients and control groups (healthy donors (HDs) and idiopathic erythroderma (IE) nodes) to investigate the inflammatory markers IL-1B and IL-18 at the protein and transcript expression levels, as potential markers of inflammasome activation. Our findings showed increased IL-1B and decreased IL-18 protein expression in the epidermis of SS patients; however, in the dermis layer, we detected increased IL-18 protein expression. In the lymph nodes of SS patients at advanced stages of the disease (N2/N3), we also detected an enhancement of IL-18 and a downregulation of IL-1B at the protein level. Moreover, the transcriptomic analysis of the SS and IE nodes confirmed the decreased expression of IL1B and NLRP3, whereas the pathway analysis indicated a further downregulation of IL1B-associated genes. Overall, the present findings showed compartmentalized expressions of IL-1B and IL-18 and provided the first evidence of their imbalance in patients with Sezary syndrome.