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MicroRNA profile in Allergic Contact Dermatitis to methylisotiazolinone

Grant number: 19/26136-2
Support Opportunities:Regular Research Grants
Duration: September 01, 2020 - August 31, 2022
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Vitor Manoel Silva dos Reis
Grantee:Vitor Manoel Silva dos Reis
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Maria Notomi Sato

Abstract

Allergic Contact Dermatitis (ACD) is a type IV hypersensitivity skin immune reaction mediated by allergen-specific T lymphocytes. Isothiazolinones include products such as methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI), which are heterocyclic compounds used as biocides due to their antimicrobial properties, present in industrial products, cosmetics and even "slimes" widely used by children. ACD to MI has increased over the years and has become an "epidemic" in European countries, in Brazil it is used as MCI: MI form, and the frequency is still underreported. Previous results from our group showed that the reaction to MCI/MI elicits a proinflammatory response with predominantly Th2 effector T cells, despite the presence of M2 macrophages and CD4+Foxp3+ regulatory T cells. Gene expression regulatory components such as microRNAs are able to play a critical role in regulating the immune response, including differentiation, proliferation, determination of cell fate, and to modulate intracellular signaling pathways. However, it is unknown whether in ACD occurs a change in miRNA profile and their association with the pathophysiology of the disease. The proposal of this project is to evaluate the profile of microRNAs (miRNAs) in the DCA reaction to MI. miRNAs sequencing will be performed in the cutaneous reaction to MI in sensitized and non-sensitized individuals exposed to the compound. miRNAs (overexpressed or under-expressed) and possible target mRNAs or proteins related to regulation of Th2-type response and inflammatory response are topics of investigation. The functional evaluation of miRNAs (mimetic or anti-miRNAs) will be verified in regulation of the CD4+ T cell activation or in the lipopolysaccharide induced inflammatory response by mononuclear cells. The study of miRNAs related to MI-induced ACD may be essential for a better understanding of immunopathogenesis and for the search for therapeutic miRNAs. (AU)

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