Protemic characterization of exosomes from plasma and dermal fibroblasts in adults with atopic dermatitis

• Grant number: 16/24161-1
• Support Opportunities: Regular Research Grants
• Duration: April 01, 2017 - September 30, 2019
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Raquel Leão Orfali
• Grantee: Raquel Leão Orfali
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Maria Notomi Sato ; Mariana Colombini Zaniboni ; Valeria Aoki

Abstract

Atopic dermatitis (AD) is an inflammatory skin disease with intense pruritus and skin xerosis. AD pathogenesis is multifactorial, involving genetic, environmental and immunological factors, among others, in addition to chronic skin colonization by Staphylococcus aureus (S. aureus) in 80-100% of patients. Exosomes are extracellular microvesicles produced by various antigen presenting cells, which has been linked to several inflammatory diseases. Recent studies show that extracellular vesicles of S. aureus in vitro, increased production of pro-inflammatory mediators (IL-6, thymic stromal lymphopoietin-TSLP, macrophage inflammatory protein-1±-MIP, and eotaxin) in dermal fibroblasts from AD patients. However, it has not been characterized the profile of plasma-derived exosomes, or dermal fibroblasts from patients with AD. Thus, our study aims to evaluate the proteomic profile of exosomes from plasma and dermal fibroblasts from adults with severe atopic dermatitis, as well as the possible influence of Staphylococcus aureus superantigens. The following evaluations will be performed: i) proteomic profile analysis of exosomes in plasma and fibroblast cultures of adult skin biopsies with AD and controls; ii) Effect of purified exosomes from plasma and dermal fibroblast cultures in the proliferative capacity of the peripheral blood mononuclear cells under stimulation with staphylococcal enterotoxin B (SEB) and phytohemagglutinin (PHA), as well as the expression of transcribed genes related to T cell anergy. These parameters may contribute to the understanding of anergic profile of T cells in adults with AD to the chronic stimulation by S. aureus and favour the search for therapeutic strategies. (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; 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; et al. Staphylococcus aureus enterotoxins modulate IL-22-secreting cells in adults with atopic dermatitis. SCIENTIFIC REPORTS, v. 8, APR 27 2018. (14/25645-7, 16/24161-1)

YAMADA YOSHIKAWA, FABIO SEITI; DE LIMA, JOSENILSON FEITOSA; SATO, MARIA NOTOMI; LEUZZI RAMOS, YASMIN ALEFE; AOKI, VALERIA; ORFALI, RAQUEL LEAO. Exploring the Role of Staphylococcus Aureus Toxins in Atopic Dermatitis. TOXINS, v. 11, n. 6, JUN 2019. (18/23211-0, 16/24161-1)

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. (16/24161-1, 14/25645-7)