Regulation of Group 2 Innate Lymphoid Cells

Jörg Hermann Fritz, PhD
Director
McGill University Research Centre on Complex Traits

Associate Professor
Department of Microbiology and Immunology
McGill University

This conference is hosted by Woong-Kyung Suh, PhD . This conference is part of the 2023-2024 IRCM conference calendar.

In person: 
IRCM Auditorium
110, avenue des Pins O, H2W 1R7 Montreal

About this conference
Group 2 innate lymphoid cells (ILC2s) comprise a remarkably potent source of cytokines and have been shown to be central in instructing and sustaining human type 2 immunopathologies including allergic lung inflammation and asthma. ILC2s directly sense alarmins such as interleukin (IL)-33 following allergen or microbial challenge, driving ILC2 proliferation and type 2 cytokine production. However, the precise molecular signatures of IL-33-mediated ILC2 activation remain unknown. Using an RNA-sequencing approach we revealed that IL-33 stimulation rapidly induces the expression of diacylglycerol acyltransferase 2 (DGAT2), an enzyme known catalyze triacylglycerol synthesis and lipid storage in lipid droplets. In addition, we observed that IL-33-mediated ILC2 activation leads to elevated fatty acid uptake and storage that requires activity of fatty acid binding protein 5 (FABP5) and fatty acid transporter protein 2 (FATP2). Importantly, lipidomic analysis revealed a selective role of DGAT2 in fatty acid metabolism in ILC2. Moreover, in a preclinical mouse model of allergic airway inflammation, we demonstrate that DGAT2 inhibition decreases ILC2 proliferation, lung inflammation and airway hyperreactivity. These observations highlight the crucial role of DGAT2 in ILC2 biology and ILC2-mediated lung inflammation and suggest that DGAT2 inhibitors should be considered for the treatment of type 2 immunopathologies.

About Jörg Hermann Fritz
Dr. Jörg H. Fritz graduated from the University of Vienna, Austria in 2004, where he received his PhD in Immunology in cooperation with the biotech start-up Intercell (now Valneva). There, he developed the vaccine adjuvant IC31, which is currently in Phase 2 and Phase 3 clinical trials of novel vaccine candidates. Following two postdoctoral training periods at the Pasteur Institute (Paris) and the University of Toronto, he joined the Department of Microbiology and Immunology at McGill University in 2010.

Since the summer of 2022, Dr. Fritz is the Director of the McGill Research Center on Complex Traits (MRCCT) and a member of the executive committee of the recently formed Institute of Genomic Medicine. Dr. Fritz's research interests are focused on how innate immunity shapes antigen-specific memory and contributes to chronic inflammatory diseases. His research in the field of cellular and molecular immunology was awarded several project grants by the Canadian Institutes of Health Research (CIHR) and the New Frontiers Research Fund (NFRF) of the Canadian government.

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