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Messing, Melina

University of British Columbia

The immune system evolved to protect the host from external pathogens as well as manage host internal processes including tissue repair after damage. This thesis explores different aspects of immune responses in the context of viral infection, allergic disease, and internal, sterile muscle injury. Firstly, the characterization of peripheral blood immune cells in patients admitted to the intensive care unit (ICU) due to an infection with SARS-CoV-2, the virus that causes COVID-19, uncovered immune biomarkers, specifically serum IL-10 and CD11cˡºʷ classical monocytes, that are predictive of disease outcome. The unprecedented and ongoing burden caused by the COVID-19 pandemic makes this research timely and critical to assist with ICU patient management. Secondly, the characterization of immune cells in archived umbilical cord blood revealed biomarkers predictive of the development of childhood allergic disease, which occurs commonly and severely and for which disease origin is unclear. Our findings suggest that alterations in naive CD8 T cells and monocytes are already established prior to birth in children who, by the age of 5, develop a combined wheeze and atopy phenotype. The stages of prenatal immune development are rarely explored in the context of allergic disease development and may be a new avenue for early disease detection and prevention. Lastly, the characterization and manipulations of type-2 immune responses in mouse models of sterile acute and chronic skeletal muscle injury showed that type-2 immune cells are largely expendable in normal tissue regeneration but accelerate muscle pathology. Specifically, IL-33- induced type-2 immunity promoted prominent influx of ILC2s and eosinophils in acutely injured skeletal muscle with no discernable impact on muscle regeneration but accelerated fibrosis deposition in mdx mice – a model of Duchenne muscular dystrophy. These findings add to our understanding of how the immune system supports normal tissue function and how tissue is damaged in disease, which is fundamental for future development of disease treatments and preventative measures.

Text

2023-09-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/82679

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/