Journal of Liver

Bone marrow monocytes sustain NK cell-poiesis during non-alcoholic steatohepatitis (NASH)

14^th International Conference on Liver Diseases & Hepatology

May 18, 2023 | Webinar

Elsa BOURAYOU

Institut Pasteur, Paris

Scientific Tracks Abstracts: J Liver

Abstract:

In western countries where the unbalanced diets are causing a rise in obesity and metabolic disease incidence, the prevalence of non-alcoholic steatohepatitis (NASH) is now skyrocketing. Yet, the pathogenesis of the different stages is still not fully known highlighting the need to further understand the cellular and molecular events underlying NASH evolution. Natural Killer (NK) cells are the predominant lymphocyte population in the liver. At the onset of NASH, an accumulation of activated NK cells has been observed in the liver in parallel with inflammatory monocyte recruitment and an increase in systemic inflammation. Using in vivo and in vitro experiments, we show that NK cells are recruited to the liver where they restrict Ly6Chigh monocyte recruitment and polarize them towards an M1 phenotype. We demonstrate that the NK cell recruitment is sustained by an IL-15-dependent increased NK cell- poiesis in the bone marrow. NK precursors are specifically stimulated through medullary monocytes that trans- present IL-15 and secrete osteopontin, a biomarker for patients with NASH. This cellular dialogue leads to increased survival and maturation of NK precursors. Endotoxemia is involved in this process and is partly responsible for the increase in osteopontin production by bone marrow monocytes.We propose a tripartite gut-liver-bone marrow axis regulating the immune population dynamics and effector functions during liver inflammation.

Biography :

I am Elsa, a PhD student in Ana Cumano’s lab, in the Immunology department of the Pasteur Institute. I graduated from the Grande École of engineering AgroParisTech but decided to pursue in research. I work on Natural Killer cells and their implication in non-alcoholic steatohepatitis (NASH) and liver diseases. My focus is on the impact the pathology has on NK cell development and maturation and how this further influences the progression of the disease