Molecular events controlling CD8+ T cell differentiation during acute and chronic responses

Nathalie Labrecque, PhD
Professor
Department of Medicine
Department of Microbiology, Infectious Diseases and Immunology
Faculty of Medicine, Université de Montréal
Maisonneuve-Rosemont Hospital Research Centre
 

This conference is part of the 2022-2023 IRCM conference calendar.

In person: 
IRCM Auditorium
110, avenue des Pins O, H2W 1R7 Montreal
Wearing a mask is mandatory at all times

Online:
Zoom Link : https://zoom.us/j/95269762104
ID : 952 6976 2104
Code : 476372

IRCM conferences are set to occur under a hybrid format. However, please note that last-minute changes to online-only lectures may occur due to unforeseen circumstances. We invite you to visit this webpage again a few days before attending.

Short bio: 
Dr. Nathalie Labrecque is a Professor in the Department of Medicine and the Department of Microbiology, Infectious Diseases and Immunology of the Université de Montréal, and a Principal Investigator at the Maisonneuve-Rosemont Hospital Research Centre (CRHMR). Her research focuses on defining the molecular events controlling effector and memory CD8+ T cell differentiation. More specifically, her laboratory is defining how the Notch signalling pathway, the NR4A orphan nuclear receptor family members and the UCH family of deubiquitinases influence CD8+ T differentiation during acute and chronic responses. In addition, her team is studying the impact of the circadian clock on T cell immunity and the role of autoreactive T cells in Parkinson’s disease. Her work has been published in renowned journals and is currently supported by CIHR, NSERC, CFI and ASAP. 

Abstract:
CD8+ T cells are potent cells of the adaptive immune system able to eradicate intracellular infections, control chronic infections and eliminate tumors. A better understanding of the mechanisms regulating their response is essential to develop new strategies to fight infections and cancer. Following antigen recognition, the rare antigen-specific CD8+ T cells massively expands and differentiate into effectors that will control the infectious agent. Two main subtypes of CD8+ effectors are generated: short-lived effector cells (SLECs) and memory precursor effector cells (MPECs). Following pathogen clearance, SLECs will undergo apoptosis while MPECs will survive and further differentiate into memory CD8+ T cells that will confer long-term protection against re-infection. Over the years, my laboratory has focused on the defining the signals and transcriptional network controlling SLEC versus MPEC cell fate choice. We have uncovered essential role for the Notch signaling pathway and the orphan nuclear receptor NR4A3 in SLEC/MPEC differentiation. In the first part of my presentation, I will discuss our recent findings on the role of Notch signaling during CD8+ T cell response to acute infection and vaccination. This will include defining: i) when the Notch signal is provided to CD8+ T cells; ii) which cell types provide the Notch ligand during CD8+ T cell response; iii) how at the molecular level Notch signaling influences SLEC differentiation. I will also present our recent work on the role of the Notch signaling pathway in the differentiation of resident memory CD8+ T cells, a unique subset of memory CD8+ T cells that established permanent residency at the site of infection. In the second part of my presentation, I will discuss the role of the Notch signaling pathway and the orphan nuclear receptor NR4A3 during chronic infection and cancer, a type of response leading to CD8+ T cell exhaustion.
 

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