JOSENILSON FEITOSA DE LIMA
Projetos de Pesquisa
Unidades Organizacionais
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
15 resultados
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- Chronic activation profile of circulating CD8+T cells in Sezary syndrome(2018) TORREALBA, Marina Passos; MANFRERE, Kelly Cristina; MIYASHIRO, Denis R.; LIMA, Josenilson F.; OLIVEIRA, Luana de M.; PEREIRA, Natalli Z.; CURY-MARTINS, Jade; PEREIRA, Juliana; DUARTE, Alberto J. S.; SATO, Maria N.; SANCHES, Jose A.Sezary syndrome (SS) is a leukemic variant of cutaneous T cell lymphoma (CTCL), and the neoplastic CD4+ T cells of SS patients undergo intense clonal proliferation. Although Sezary cells have been studied extensively, studies on adaptive immunity regarding CD8+ T cells are scarce. This study aimed to investigate activation marker expression in CD8+ T cells according to the differentiation stages and IL-7/IL7Ra axis responses of patients with SS. Moreover, this study aimed to verify the soluble forms of CD38, sCD127 and IL-7 in serum. Although the SS patients of our cohort had reduced numbers of CD8+ T cells, they exhibited higher percentages of CD8+CD38+T cells, mainly effector/memory CD8+ T cells, than the control group. In contrast, down-regulated expression of the activation markers CD127/IL-7R and CD26 was found in the CD8+ T cells of SS patients. High serum levels of sCD38 and sCD127 and scarce serum levels of IL-7 were detected, emphasizing the immune activation status of SS patients. Moreover, CD8+ T cells from SS patients exhibited IL-7 unresponsiveness to STAT5 phosphorylation and Bcl-2 expression, and IL-7 priming partially restored IFN gamma production. Our findings showed a chronic activation profile of CD8+ T cells, as an attenuated cytotoxic profile and impaired IL-7 responsiveness was observed, suggesting chronic activation status of CD8+ T cells in SS patients.
- 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, ValeriaStaphylococcus 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 20 Citação(ões) na Scopus Distinct Natural Killer Cells in HIV-Exposed Seronegative Subjects With Effector Cytotoxic CD56(dim) and CD56(bright) Cells and Memory-Like CD57(+)NKG2C(+)CD56(dim) Cells(2014) LIMA, Josenilson F.; OLIVEIRA, Luanda M. S.; PEREIRA, Natalli Z.; MITSUNARI, Gabrielle E.; DUARTE, Alberto J. S.; SATO, Maria N.Background: Innate immunity, including natural killer (NK) cells, may play a significant role in maintaining natural resistance to infection in highly HIV-exposed seronegative (HESN) subjects. The differences between NK-cell subsets, regarding their activating/maturing marker expression and their memory markers, in HESN subjects are not fully defined. Methods: We have conducted an analysis of the activating/memory markers and intracellular CD107a and interferon gamma (IFN-gamma) expression in NK-cell subsets from HESN and HIV-infected and healthy subjects. Results: HESN individuals showed an increased expression of activating markers, such as NKG2D in CD56(bright) and CD56(dim) NK cells, and an increased frequency of CD56(bright)CD127(+) and fully mature CD56(dim)CD57(+) NK cells compared with HIV-infected patients and healthy control subjects. Of note, HESN individuals showed an increased frequency of memory CD56(dim)CD57(+) NK cells, and this is known to be expanded on cytomegalovirus infection, as evidenced by their high rate of cytomegalovirus seropositivity. Simultaneous expression of the CD94, NKG2A, NKG2C, and NKG2D receptors on CD56(bright) NK cells was detected in HESN subjects, whereas in the HIV-1 group, the expression of these 4 receptors was enhanced in CD56(dim) NK cells. It was also found that CD56(bright) and CD56(dim) NK cells in HESN subjects showed increased CD107a and/or IFN-g expression. Conclusions: The NK cells from HESN individuals presented a unique activation profile, with increased expression of NKG2D, CD107a, and IFN-g and ""memory"" CD57(+) CD56(dim) NK cells. The complex network of functional NK-cell activities in HESN individuals may be exploited for long-term protection through vaccination.conferenceObject 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.- Upregulation of Innate Antiviral Restricting Factor Expression in the Cord Blood and Decidual Tissue of HIV-Infected Mothers(2013) PEREIRA, Natalli Zanete; CARDOSO, Elaine Cristina; OLIVEIRA, Luanda Mara da Silva; LIMA, Josenilson Feitosa de; BRANCO, Anna Claudia Calvielli Castelo; RUOCCO, Rosa Maria de Souza Aveiro; ZUGAIB, Marcelo; OLIVEIRA FILHO, Joao Bosco de; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiPrograms for the prevention of mother-to-child transmission of HIV have reduced the transmission rate of perinatal HIV infection and have thereby increased the number of HIV-exposed uninfected (HEU) infants. Natural immunity to HIV-1 infection in both mothers and newborns needs to be further explored. In this study, we compared the expression of antiviral restricting factors in HIV-infected pregnant mothers treated with antiretroviral therapy (ART) in pregnancy (n=23) and in cord blood (CB) (n=16), placental tissues (n=10-13) and colostrum (n=5-6) samples and compared them to expression in samples from uninfected (UN) pregnant mothers (n=21). Mononuclear cells (MNCs) were prepared from maternal and CB samples following deliveries by cesarean section. Maternal (decidua) and fetal (chorionic villus) placental tissues were obtained, and colostrum was collected 24 h after delivery. The mRNA and protein expression levels of antiviral factors were then evaluated. We observed a significant increase in the mRNA expression levels of antiviral factors in MNCs from HIV-infected mothers and CB, including the apolipoprotein B mRNA-editing enzyme 3G (A3G), A3F, tripartite motif family-5 alpha (TRIM-5 alpha), TRIM-22, myxovirus resistance protein A (MxA), stimulator of interferon (IFN) genes (STING) and IFN-beta, compared with the levels detected in uninfected (UN) mother-CB pairs. Moreover, A3G transcript and protein levels and alpha-defensin transcript levels were decreased in the decidua of HIV-infected mothers. Decreased TRIM-5 alpha protein levels in the villi and increased STING mRNA expression in both placental tissues were also observed in HIV-infected mothers compared with uninfected (UN) mothers. Additionally, colostrum cells from infected mothers showed increased tetherin and IFN-beta mRNA levels and CXCL9 protein levels. The data presented here indicate that antiviral restricting factor expression can be induced in utero in HIV-infected mothers. Future studies are warranted to determine whether this upregulation of antiviral factors during the perinatal period has a protective effect against HIV-1 infection.
- Proinflammatory profile of neonatal monocytes induced by microbial ligands is downmodulated by histamine(2019) BRANCO, Anna Claudia Calvielli Castelo; PEREIRA, Natalli Zanete; YOSHIKAWA, Fabio Seiti Yamada; OLIVEIRA, Luanda Mara da Silva; TEIXEIRA, Franciane Mouradian Emidio; OLIVEIRA, Luana de Mendonca; PIETROBON, Anna Julia; TORREALBA, Marina Passos; LIMA, Josenilson Feitosa de; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiAlthough the neonatal period is characterized by relative immunological immaturity, an inflammatory response due to Toll-like receptor (TLR) activation is observed. Histamine may be one of the factors playing a role in restraining inflammation during the early stages of life. Therefore, we evaluated the responsiveness of human cord blood cells to TLR4 agonists and the immunomodulatory function of histamine in the inflammatory response. Compared with adults, mononuclear cells (MNCs) from newborns (NBs) exhibit impaired production of IFN-gamma-inducible chemokines, such as CXCL10 and CXCL9, upon lipopolysaccharide (LPS) stimulation. Notably, LPS induced a 5-fold increase in CCL2 secretion in NBs. Evaluation of the effect of histamine on LPS-induced CCL2 secretion showed an inhibitory effect in the majority of adults, whereas this effect was detectable in all NBs. Histamine receptor (HR) blockage revealed partial involvement of H1R, H2R and H4R in LPS-induced CCL2 inhibition in MNCs from both NBs and adults. As monocytes are the main type of mononuclear cell that produces CCL2, we evaluated genes related to TLR signaling upon LPS stimulation. Monocytes from NBs showed up-regulation of genes associated with JAK/STAT/NF-kappa B and IFN signaling. Some differentially expressed genes encoding proinflammatory factors were preferentially detected in LPS-activated monocytes from NBs, and markedly down-regulated by histamine. The immunomodulatory role of histamine on CCL2 and CXCL8 was detected at the transcript and protein levels. Our findings show that NBs have enhanced CCL2 responsiveness to LPS, and that histamine acts in immune homeostasis during the neonatal period to counterbalance the robustness of TLR stimulation.
- Increased frequency of circulating Tc22/Th22 cells and polyfunctional CD38(-) T cells in HIV-exposed uninfected subjects(2015) OLIVEIRA, Luanda M. S.; LIMA, Josenilson F.; CERVANTES, Cesar A. C.; CASSEB, Jorge S.; MENDONCA, Marcelo; DUARTE, Alberto J. S.; SATO, Maria N.Some individuals are resistant to HIV-1 infection despite repeated exposure to the virus, suggesting the presence of a complex antiviral response. Innate factors like IL-22 exert gut mucosal protection and polyfunctional T cells have been associated with low progression in HIV infection; therefore, we evaluated the frequencies of CD4+ and CD8+ T cell-secreting cytokines, including Tc22/Th22 cells and polyfunctional T cells in HIV-1-exposed uninfected individuals (EUs), their HIV-1-infected partners and healthy controls. EUs exhibited an increased frequency of p15 Gag CD4+ IL-22+ secreting T cells, whereas HIV-infected partners demonstrated a high frequency of CD4+ IL-17+ T cells in response to p24. Similar responses of Th22 and Tc22 cells to Gag peptides and Staphylococcal enterotoxin B (SEB) stimulation were detected in the serodiscordant couples. However, polyfunctionality in HIV subjects was associated with an HIV Gag response of CD38+ T cells, whereas polyfunctionality for EUs was induced upon SEB stimulation by CD38-T cells. EUs demonstrated the presence of Tc22/Th22 cells and polyfunctional CD38-T cells with a low activation profile. These data suggest that SEB-induced polyfunctional CD4+ and CD8+ T cells together with Tc22/Th22 cells in EU individuals can provide an immunological advantage in the response to pathogens such as HIV-1.
conferenceObject Phenotypic profile of CLA plus natural killer cells in adults with atopic dermatitis(2018) ORFALI, R. L.; LIMA, J. F.; CARVALHO, G. C. C.; RAMOS, Y. A. L.; DUARTE, A. J. S.; SATO, M.; AOKI, V.- Exploring the Role of Staphylococcus Aureus Toxins in Atopic Dermatitis(2019) YOSHIKAWA, Fabio Seiti Yamada; LIMA, Josenilson Feitosa de; SATO, Maria Notomi; RAMOS, Yasmin Alefe Leuzzi; AOKI, Valeria; ORFALI, Raquel LeaoAtopic dermatitis (AD) is a chronic and inflammatory skin disease with intense pruritus and xerosis. AD pathogenesis is multifactorial, involving genetic, environmental, and immunological factors, including the participation of Staphylococcus aureus. This bacterium colonizes up to 30-100% of AD skin and its virulence factors are responsible for its pathogenicity and antimicrobial survival. This is a concise review of S. aureus superantigen-activated signaling pathways, highlighting their involvement in AD pathogenesis, with an emphasis on skin barrier disruption, innate and adaptive immunity dysfunction, and microbiome alterations. A better understanding of the combined mechanisms of AD pathogenesis may enhance the development of future targeted therapies for this complex disease.
- Staphylococcus aureus enterotoxins modulate IL-22-secreting cells in adults with atopic dermatitis(2018) ORFALI, Raquel Leao; OLIVEIRA, Luanda Mara da Silva; LIMA, Josenilson Feitosa de; CARVALHO, Gabriel Costa de; RAMOS, Yasmim Alefe Leuzzi; PEREIRA, Natalli Zanete; PEREIRA, Naiura Vieira; ZANIBONI, Mariana Colombini; SOTTO, Mirian Nacagami; DUARTE, Alberto Jose da Silva; SATO, Maria Notomi; AOKI, ValeriaAtopic dermatitis (AD) is a chronic inflammatory immune-mediated skin disease characterized by skin colonization by Staphylococcus aureus. Interleukin (IL)-22, in cooperation with IL-17, triggers antimicrobial peptide elaboration and enhances certain immunological responses. In AD, IL-22 is related to epidermal hyperplasia, keratinocyte apoptosis, and inhibition of antimicrobial peptide (AMP) production. We aimed to evaluate the impact of staphylococcal enterotoxins on the Tc22/Th22 induction in the peripheral blood of AD patients and on CD4(+/)CD8(+)T cells expressing IL-22 in AD skin. Our study showed inhibition of the staphylococcal enterotoxins A and B (SEA and SEB) response by Th22 (CD4(+)IL22(+)IL-17A(-)IFN-gamma(-)) cells in AD patients. In contrast, Tc22 (CD8(+)IL-22(+)IL-17A(-)IFN-gamma(-)) cells were less susceptible to the inhibitory effects of staphylococcal enterotoxins and exhibited an enhanced response to the bacterial stimuli. In AD skin, we detected increased IL-22 transcript expression and T lymphocytes expressing IL-22. Together, our results provide two major findings in response to staphylococcal enterotoxins in adults with AD: dysfunctional CD4(+)IL-22 secreting T cells and increased Tc22 cells. Our hypothesis reinforces the relevance of CD8 T cells modulated by staphylococcal enterotoxins as a potential source of IL-22 in adults with AD, which is relevant for the maintenance of immunological imbalance.