Investigation of the role of non-canonical autophagy in IL-4Ra signaling in response to efferocytosis

• Grant number: 25/06271-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2025
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Larissa Dias da Cunha
• Grantee: Mateus dos Reis Zuba dos Santos
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 18/25559-4 - Molecular mechanisms of LC3-associated phagocytosis and its role in macrophage function, AP.JP

Abstract

Inflammatory responses induced by infectious agents or sterile insults cause tissue damage that must be repaired as part of a pro-resolution program to allow functional regeneration and return to homeostasis. Macrophages play a fundamental role in this resolution process by secreting mediators with anti-inflammatory and pro-tissue repair effects. Additionally, macrophages act as effector cells in the removal of dead cells, a process known as efferocytosis. There is an association between efferocytosis and signaling triggered by Th2 cytokines IL-4 and IL-13 through the IL-4 receptor alpha (IL-4R¿), promoting the genetic programming of macrophages for tissue repair functions. However, the mechanisms responsible for integrating these signals remain unknown. The efficient degradation of dead cells by macrophages occurs through a non-canonical autophagy process called LC3-associated phagocytosis (LAP), in which ATG8 family proteins, such as LC3, are conjugated to the membrane of the phagosome containing the cargo to be degraded. In this project, we aim to investigate the mechanisms associated with controlling the pro-resolutive function of macrophages in the context of efferocytosis. Our hypothesis is that the induction of non-canonical autophagy during efferocytosis regulates the genetic reprogramming of macrophage anti-inflammatory and tissue repair functions associated with the resolution process. Based on this, our objective is to study the role of non-canonical autophagy in IL-4R¿ signaling in response to efferocytosis. (AU)