MARIANA COLOMBINI ZANIBONI
Projetos de Pesquisa
Unidades Organizacionais
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
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- Skin barrier in atopic dermatitis: beyond filaggrin(2016) ZANIBONI, Mariana Colombini; SAMORANO, Luciana Paula; ORFALI, Raquel Leao; AOKI, ValeriaAtopic dermatitis is a chronic inflammatory skin disease with a complex pathogenesis, where changes in skin barrier and imbalance of the immune system are relevant factors. The skin forms a mechanic and immune barrier, regulating water loss from the internal to the external environment, and protecting the individual from external aggressions, such as microorganisms, ultraviolet radiation and physical trauma. Main components of the skin barrier are located in the outer layers of the epidermis (such as filaggrin), the proteins that form the tight junction (TJ) and components of the innate immune system. Recent data involving skin barrier reveal new information regarding its structure and its role in the mechanic-immunological defense; atopic dermatitis (AD) is an example of a disease related to dysfunctions associated with this complex.
- Profile of skin barrier proteins (filaggrin, claudins 1 and 4) and Th1/Th2/Th17 cytokines in adults with atopic dermatitis(2015) BATISTA, D. I. S.; PEREZ, L.; ORFALI, R. L.; ZANIBONI, M. C.; SAMORANO, L. P.; PEREIRA, N. V.; SOTTO, M. N.; ISHIZAKI, A. S.; OLIVEIRA, L. M. S.; SATO, M. N.; AOKI, V.BackgroundAtopic dermatitis (AD) in adults and profile of skin barrier proteins and inflammatory cytokines. ObjectiveEvaluation of the expression of skin barrier proteins such as filaggrin, claudins 1 and 4 and of circulating inflammatory cytokines (Th1/Th2/Th17) in adults with AD. MethodsThirty-three adult patients with AD diagnosed according to the Hanifin & Rajkacriteria, and 25 healthy controls were enrolled in the study. AD severity was measured by Eczema Area and Severity Index (EASI). Laboratory assays included immunohistochemistry analysis of skin barrier proteins, such as filaggrin, claudins 1 and 4 and interleukin-17 (IL-17) from skin samples and determination of circulating cytokine levels (IL-2, 4, 5, 6, 10, 17A, TNF and IFN-) by flow cytometry (Cytometric Bead Array). ResultsWe observed a reduced expression of filaggrin and claudin 1 in lesional skin of AD patients, when compared to controls. There was an inverse correlation of filaggrin expression and disease severity. In addition, IL-17 expression was enhanced in AD patients. Similarly, higher levels of inflammatory cytokines (IL-2, 5, 6, 10, 17A and IFN-) were found in AD patients. ConclusionOur data reinforce the role of an altered skin barrier in the pathogenesis of AD. Our results show not only reduced expression of filaggrin and claudin 1 in lesional atopic skin but also inverse correlation of filaggrin expression and disease severity. Moreover, elevation of in situ IL-17 and of circulating interleukin levels in AD emphasize the systemic, inflammatory profile of this defective skin barrier dermatosis.
- Profile of skin barrier proteins and cytokines in adults with atopic dermatitis(2017) ORFALI, Raquel L.; ZANIBONI, Mariana C.; AOKI, ValeriaAtopic dermatitis (AD), an inflammatory skin disorder with chronic course and characterized by intense pruritus, is a dermatosis of high prevalence of childhood. However, persistence of the disease in adolescents and adults may occur, and more studies regarding the interactions of the complex triggering factors, especially between the adaptive and innate immune alterations and skin barrier defects are needed. In this review the authors summarize the major novel findings of a dysfunctional skin barrier in AD, with emphasis on tight junction components, such as claudins and on proteins of the keratinocyte differentiation, such as filaggrin. This review also provides an update on the characterization of immune response in adults with atopic dermatitis. The adaptive immune dysfunction in AD, classically known as a Th2/Th1 model, has changed its profile, with recent reported cytokines such as interleukins 17, 22, and 31; as for the innate immune system scenario in AD, the characterization of skin microbiome opens new frontiers for the understanding of such a complex inflammatory 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.
- Up-regulation of HMGB1 and TLR4 in skin lesions of lichen planus(2018) CARVALHO, Gabriel Costa de; HIRATA, Fabiana Yasumoto Araujo; DOMINGUES, Rosana; FIGUEIREDO, Cristina Adelaide; ZANIBONI, Mariana Colombini; PEREIRA, Naiura Vieira; SOTTO, Mirian Nacagami; AOKI, Valeria; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiLichen planus (LP) is a chronic, mucocutaneous inflammatory disease of an unknown aetiology. The disease has been associated with certain viruses, and the factors such as DAMPs (damage-associated molecular patterns) and PAMPs (pathogen-associated molecular patterns) may also contribute to the inflammatory response in LP. HMGB1 (high mobility group box 1 protein) is one of the major DAMPs that induces inflammation and could trigger LP disease. The present study was aimed to examine TLR4, RAGE and HMGB1 production in epidermis or dermis by immunohistochemistry and the respective expression of these targets in the skin lesions of patients with LP. Moreover, we measured HMGB1 serum levels by ELISA. The results showed similar profile of expression by HMGB1 and TLR4, which are decreased at epidermis and up-regulated at dermis of skin lesions of LP patients that was sustained by intense cellular infiltration. RAGE expression was also increased in dermis of LP. Although there is increased RAGE protein levels, a decreased RAGE transcript levels was detected. Similar HMGB1 serum levels were detected in the LP and control groups. This study demonstrates that HMGB1 and TLR4 could contribute to the inflammatory LP process in skin.