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Analysis of the pattern recognition receptors and crosstalk between dendritic cells-T lymphocytes and macrophages in allergic contact dermatitis by methylisothiazolinone and methylchloroisothiazolinone

Grant number: 17/12475-4
Support type:Regular Research Grants
Duration: September 01, 2017 - November 30, 2019
Field of knowledge:Biological Sciences - Immunology
Principal researcher:Vitor Manoel Silva dos Reis
Grantee:Vitor Manoel Silva dos Reis
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers: Anangélica Rodrigues Virgens ; Gabriel Costa de Carvalho ; Heliana Freitas de Oliveira Góes ; Maria Notomi Sato

Abstract

Allergic contact dermatitis (ACD) is one of the most common inflammatory skin diseases mediated by the type IV hypersensitivity reaction after contact with the allergen. Usually, they are haptens, which form complexes with proteins for sensitization. Methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) are widely used as preservatives and recently has been occurred a significant increase in ACD triggered by cosmetics. However, there are few studies regarding the immunological mechanism of ACD by MCI and MI, especially on the influence of innate immunity. The aim of this study is to evaluate whether MCI/MI is capable to activate via pattern recognition receptors (PRRs) such as Toll-like receptor 4 and inflammasomes, as well as to evaluate the in situ expression of PRRs and the interaction between dendritic cells, T lymphocytes and macrophages and their subtypes in the DCA by MCI/MI. For this purpose, reactor individuals to MCI/MI in the patch test will be enrolled at the Dermatology Ambulatory of the HC-FMUSP. The skin biopsies will be performed in the elicitation phase of the positive reaction for MCI/MI, as well as of non-reactor individuals as control group. The transcriptional and protein profile of TLR4 and the inflammasome components NLRP3, AIM-2 and IL-1-² will be evaluated in the biopsies of the patch test. Moreover, the presence of macrophage subtypes (M1 CD68+Stat1+/M2 cMAF+CD68+) by immunohistochemistry and the likely cluster formation between dendritic cells - T lymphocytes or dendritic cells - macrophages - T lymphocytes by immunofluorescence will be analyzed. In addition, it will be evaluated whether MCI/MI can activate via TLR4 and inflammasomes in peripheral blood mononuclear cells and keratinocytes lineage using inhibitors of TLR4 and inflammasomes in the secretion of cytokines (IL-², IL-17, IL-22, TNF, IL1², IL-6, IL-12 e IL-10) and chemokines (CXCL2 and CXCL10). Advances in the specific knowledge of the immune mechanisms involved in the development of ACD by MCI/MI may improve the understanding of the clinical features of ACD by these compounds, in addition to enabling the search for new therapeutic targets. (AU)

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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)
VIRGENS, ANANGELICA R.; GOES, HELIANA F. O.; DE CARVALHO, GABRIEL C.; PIETROBON, ANNA JULIA; C. C. BRANCO, ANNA CLAUDIA; RAMOS, YASMIM A. L.; PEREIRA, NAIURA V.; ORFALI, RAQUEL L.; AOKI, VALERIA; DA SILVA, LUIZ FERNANDO F.; SOTTO, MIRIAN N.; DOS REIS, VITOR M. S.; SATO, MARIA N. Perivascular clusters of Th2 cells and M2 macrophages in allergic contact dermatitis to methylchloroisothiazolinone and methylisothiazolinone. EXPERIMENTAL DERMATOLOGY, AUG 2021. Web of Science Citations: 0.
DE OLIVEIRA GOES, HELIANA FREITAS; VIRGENS, ANANGELICA RODRIGUES; DE CARVALHO, GABRIEL COSTA; PIETROBON, ANNA JULIA; CALVIELLI CASTELO BRANCO, ANNA CLAUDIA; DA SILVA OLIVEIRA, LUANDA MARA; FERNANDES, IARA G.; PEREIRA, NAIURA VIEIRA; SOTTO, MIRIAN NACAGAMI; SILVA DOS REIS, VITOR MANOEL; SATO, MARIA NOTOMI. Proinflammatory and regulatory mechanisms in allergic contact dermatitis caused by methylchloroisothiazolinone and methylisothiazolinone. EXPERIMENTAL DERMATOLOGY, v. 29, n. 5 APR 2020. Web of Science Citations: 0.

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