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Importance of ERK5 in the differentiation and function of regulatory T cells

Grant number: 20/11372-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): February 01, 2021
Effective date (End): March 31, 2024
Field of knowledge:Biological Sciences - Pharmacology
Principal researcher:José Carlos Farias Alves Filho
Grantee:Marcos Henrique Rosa
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Regulatory FoxP3+ T cells (tregs) play crucial suppressive functions homeostasis of immune system homeostasis. It has been widely demonstrated that the molecular mechanisms of signaling by different stimuli are important for the proliferation, differentiation and function of Tregs. TGF-² is a crucial cytokine for FoxP3 expression, a necessary transcription factor for the differentiation, maintenance and function of Tregs. Although the signaling pathways activated by TGF-B capable of modular differentiation of Tregs are not fully understood. ERK5 (kinase regulated by extracellular signal 5) is an atypical member of the MAPK family, since it has the functions of kinase and also the role of regular activity of transcription factors independent of its kinase function. It is known that ERK5 is activated in different cell types by TGF-B, but it has nothing described with its involvement in Treg lymphocytes. However, the preliminary data from our laboratory demonstrated that the ERK5 is important in differentiating Tregs. Therefore, this project aims to understand the role of ERK5 in the differentiation and function of Tregs. The project has an innovative proposal using single cell RNA sequencing, metabolome and proteome to unravel the real role of ERK5 in Tregs, which can provide possible targets for the development of therapies for inflammatory and autoimmune diseases. (AU)

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