The role of natural killer T cells on liver homeostasis

• Grant number: 21/11200-7
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2022
• End date: February 29, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandre de Castro Keller
• Grantee: Alexandre de Castro Keller
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Flávio Aimbire Soares de Carvalho ; Gustavo Batista de Menezes ; Richardt Gama Landgraf
• Associated research grant(s): 22/00181-4 - The interplay between intestinal neuroimmune circuits and iNKT in the physiology of the gut/liver axis, AP.R SPRINT

Abstract

The liver is responsible for several vital functions, and due to its physiological and anatomical characteristics, it is a constant target of different injuries. In this context, the magnitude and duration of the inflammatory process associated with tissue damage directly impact liver physiology. Given the direct relationship between inflammation and the activation of the immune system, it is essential to understand the immune mechanisms that regulate liver physiology. As this organ is particularly rich in Natural Killer T cells (NKT), we intend to use models of autoimmune liver injury and liver injury secondary to infections to clarify how these cells are activated during the inflammatory process and the mechanisms influencing the liver damage. Besides contributing to the understanding of liver physiology, we sought to determine new prognostic factors and possible therapeutic alternatives for immune-mediated liver diseases. Moreover, it is noteworthy that NKT cells are a potential target for immunotherapy against several diseases, especially cancer; however, their activation by exogenous stimuli results in liver injury, a limiting factor for this approach. Therefore, understanding this phenomenon is an essential contribution to the advancement of NKT cell-based immunotherapy. (AU)