Importance of IL-33 in the development of Wallerian degeneration and its actions on immune cells

• Grant number: 21/10494-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2022
• Status: Discontinued
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Thiago Mattar Cunha
• Grantee: Gabriel Victor Lucena da Silva
• 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): 24/07534-5 - The role of group 2 innate lymphoid cells producing GM-CSF in homeostasis and inflammation, BE.EP.DR

Abstract

Wallerxian degeneration (WD) is an important process of myelin destruction and destruction after a mechanical trauma after a trauma, or immune in the peripheral system, being important for the functional recovery of the tissue afterwards. The cytokine IL-33 belongs to the IL-1 superfamily group and is expressed by hematopoietic cells and has already been described as being important in different tissues. In relation to the nervous system, IL-3 was described, being important for the evaluation of the spinal cord afterwards. There have not yet been reports of the existence of IL-33 or the mechanism that it participates in the peripheral nervous system, and there is even a lack of information about the involvement of IL-33 during DW. Our group depends on the presence of IL-3 associated with sciatic nerve injury and does not elucidate the local nerve of the cellular source of IL-3, or 33 the local nerve of mesenchymal cells. Given these findings, our hypothesis that it is not a target of a DW process for IL-33 leukocytes, an important function in the recruitment of immune cells via the receptor and also activates ST2 cells, increased the degenerative process. For this, we will use animals deficient for IL-33 or for its ST2 receptor and we will induce the sciatic nerve destruction model (CNI), the sciatic functionality index (SFI); balance/locomotive ability with Rotarod; painful with mechanical and thermal tests. In addition, we will use histological techniques to observe tissue organization, remyelination, after CNI and flow cytometry on different days to characterize the cell infiltrate at the inflammatory site in the sciatic nerve. since it is present in several immune cells, we will study the resident macrophage, expressing the ST receptor during CNI, and we will investigate whether the ST receptor then-33 is important for IL2 in these cells. Finally, we will evaluate the presence of IL-33 in terms of manipulated manipulation in order to validate whether the mechanisms that will be observed in animal models also occur in human specimens.