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

• Grant number: 20/11372-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: February 01, 2021
• End date: March 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: José Carlos Farias Alves Filho
• Grantee: Marcos Henrique Rosa
• Host 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
• Associated scholarship(s): 23/02431-0 - Elucidating the role of ERK5 in the regulation of autophagy in regulatory T cells, BE.EP.DR

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)