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Evaluation of inflammatory dendritic cells and T cells in adults with atopic dermatitis

Grant number: 14/25645-7
Support type:Regular Research Grants
Duration: April 01, 2016 - March 31, 2018
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Valeria Aoki
Grantee:Valeria Aoki
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Josenilson Feitosa de Lima ; Maria Notomi Sato ; Raquel Leão Orfali

Abstract

Atopic dermatitis (AD) is an inflammatory, chronic and recurrent skin disease characterized by intense pruritus and xerosis. AD has a complex etiopathogenesis, which involves the influence of genetics, environment, and immunological disorders, among others. AD is a disease of the skin barrier, which leads to altered physic-chemical and immunological dysfunction.In AD, there is a chronic cutaneous colonization of Staphylococcus aureus (S. aureus). Toxins and enterotoxins produced by Staphylococcus aureus (S. aureus) may trigger inflammation through innate or adaptive immunity. Keratinocytes and dendritic cells (DC) express receptors of molecular recognition associated to pathogens, the so-called toll-like receptors (TLR). Individuals with AD show dysfunctional TLR and antimicrobial peptides, therefore favoring S. aureus infection. Dendritic cells exert a relevant role in the inflammatory response of AD, especially the inflammatory dendritic epidermal cells (IDEC). Natural killer (NK) cells are described as capable of regulate immunological response but their role in AD remains unclear. However, the profile of DC and NK in peripheral blood and their close relationship to staphylococcal enterotoxins need to be further evaluated in AD patients. Dysfunctional Th1 and Th2 cells and their pathogenic role have been described in AD. New T cell subsets such as Th17 and Th22 cells still have controversial role in AD. Therefore, our study aims to evaluate the innate immunity through analysis of myeloid dendritic cells (mDC) and NK, as well as the adaptive immunity, by evaluating the Th22 / CD4 + and Tc22 / CD8 + cells in response to staphylococcal enterotoxins.The innate response in AD will be assessed by phenotypical analysis of mDC, which includes the expression of surface molecules CD11c, HLA-DR, CD83, high affinity IgE receptor (FcµRI) and scavenger receptor CD36, the last two being used as markers of inflammatory epidermal dendritic cells (IDEC). Functional evaluation of mDC will be assessed by intracellular expression of TNF-±, IFN-³ and IL-10 on peripheral blood mononuclear cells (PBMC) by flow cytometry. IDEC will be further characterized in skin biopsies using immunohistochemistry. Moreover, functional and phenotypic profile of NK cells stimulated with polyclonal activators and staphylococcal enterotoxin B (SEB), will be evaluated by expression of cell activation markers and cytokine secretion by flow cytometry. The adaptive response in AD will be explored through evaluation of Tc22 and Th22 cells stimulated with SEA and SEB by flow cytometry. Innate and adaptive immune parameters, beyond offering a better comprehension of AD pathogenesis may contribute to the development of new therapeutic targets. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ORFALI, RAQUEL LEAO; YAMADA YOSHIKAWA, FABIO SEITI; DA SILVA OLIVEIRA, LUANDA MARA; PEREIRA, NATALLI ZANETE; DE LIMA, JOSENILSON FEITOSA; LEUZZI RAMOS, YASMIM ALEFE; DA SILVA DUARTE, ALBERTO JOSE; SATO, MARIA NOTOMI; AOKI, VALERIA. Staphylococcal enterotoxins modulate the effector CD4(+)T cell response by reshaping the gene expression profile in adults with atopic dermatitis. SCIENTIFIC REPORTS, v. 9, SEP 11 2019. Web of Science Citations: 0.
ORFALI, RAQUEL LEAO; DA SILVA OLIVEIRA, LUANDA MARA; DE LIMA, JOSENILSON FEITOSA; DE CARVALHO, GABRIEL COSTA; LEUZZI RAMOS, YASMIM ALEFE; PEREIRA, NATALLI ZANETE; PEREIRA, NAIURA VIEIRA; ZANIBONI, MARIANA COLOMBINI; SOTTO, MIRIAN NACAGAMI; DA SILVA DUARTE, ALBERTO JOSE; SATO, MARIA NOTOMI; AOKI, VALERIA. Staphylococcus aureus enterotoxins modulate IL-22-secreting cells in adults with atopic dermatitis. SCIENTIFIC REPORTS, v. 8, APR 27 2018. Web of Science Citations: 5.
DOS SANTOS, VANESSA G.; ORFALI, RAQUEL L.; TITZ, TIAGO DE OLIVEIRA; DUARTE, ALBERTO J. DA SILVA; SATO, MARIA N.; AOKI, VALERIA. 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. INTERNATIONAL JOURNAL OF DERMATOLOGY, v. 56, n. 6, p. 630-635, JUN 2017. Web of Science Citations: 3.

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