The pandemic of obesity is growing as unhealthy food habits continue to spread around the world. After that, the incidence of non-alcoholic steatohepatitis (NASH), an inflammatory liver condition. Although the meaning of the immune system is known to be crucial in NASH, many mechanisms are yet to be revealed. Among the large liver immune cells, there are natural killer (NK) cells, which are the most determined defenders of the liver.
A recent collaborative research effort led by Professor Rachel Golub and Elsa Bourayou from the University of Pasteur-Paris Cité , characterizes the role of hepatic NK cells during NASH and reveals the critical role of bone marrow monocytes in NK cell development in this case. This important study published in the Cell Report explores complex cellular interactions that are essential for maintaining liver health and managing immune responses in NASH.
The NASH stage is characterized by the accumulation of fat in the liver and the damage to liver cells. Today, Nash is considered an urgent health problem worldwide and poses a risk of developing cirrhosis or liver cancer without effective management. However, understanding of the evolution and pathogenesis of this complex disease remains a difficult problem in the medical community. This study explores the role of bone marrow action in regulating immune responses during Nash, an important step in solving this puzzle.
During NASH, some signals are caused by certain signals caused by endotoxinemia (caused by elevated blood levels of endotoxins, which are usually due to intestinal bacteria entering the bloodstream – activation of bone marrow single Nuclear cells, thus increasing their production. -15/IL-15Rα complex and osteopontin. These molecules are essential for the maturation and survival of NK cell precursors and monocytes in the bone marrow, respectively. Their increased levels promote Enhanced NK cell poiesis maintains recruitment of NK cells to the liver. Where NK cells help reduce fibrosis and turn the polarization of liver monocytes into a proinflammatory state, delaying the advent of tissue scars.
This study is not only notable because it elucidates the critical role of bone marrow monocytes in regulating immune landscapes during regulation of Nash, but also proposes a complex interaction between the intestine, liver and bone marrow. The tripartite axis effectively coordinates the dynamics and functions of different immune cell populations and provides a new perspective for controlling liver inflammation.
This study specifically involves innovative and methodical approaches to understand Nash’s complex mechanisms. The team used a variety of experimental models, including dietary models, to induce mouse Nash, which reflects the development of the human condition. This approach provides a realistic context for studying disease progression and immune response. Through detailed analysis of different cell populations and measurements of specific proteins and cytokines, the team was able to dissect the complex interactions between bone marrow NK cells and monocytes in the context of chronic liver disease.
Professor Gorub reflects on the depth and breadth of their research, emphasizing the change nature of their discoveries. “During NASH, endotoxinemia-derived signals activate medullary monocytes, which upregulate the IL-15/IL-15RA complex and osteopontin, promoting the maturation and survival of NK precursors. . These NK precursors exit from the bone marrow and connect the liver, where they inhibit fibrosis and polarize recruited monocytes toward the M1-like phenotype. “This emphasizes the good coordination of the intestinal bone bone bone axis in effective management Key roles in liver inflammation and fibrosis and point out potential new therapeutic targets.
In summary, this model of integrated inter-organizational communication marks a huge advance in liver disease research.
Journal Reference
Elsa Bourayou, Thibaut Perchet, Sylvain Meunier, Hugo Bouvier, Marie-Pierre Mailhe, Evie Melanitou, Ana Cumano, Rachel Golub, Rachel Golub, “Bone Marrow Monocyte Maintain NK Cell-Poiesis in non-alcoholic steatoholic Hoceoholic poiesis.
doi: https://doi.org/10.1016/j.celrep.2024.113676.
About the Author
Professor Rachel Gorub As a leader in the “Development of Innate Lymphoid Cells (ILC) and Inflammation” research group, it is at the forefront of immunology research. With a career dedicated to uncovering the complexity of the immune system, her pioneering work has improved our understanding of hematopoiesis. Her contribution to the field began with her insight into the fetal compartment of hematopoietic stem cells and the mechanisms of hematopoietic in the fetal spleen. These early findings laid the foundation for her subsequent research efforts that increasingly focused on the biology of ILC. Professor Golub’s research highlights the key functions of Notch signaling pathways in cloning ILC precursor differentiation during fetal and adult life. This work not only deepens our understanding of immune cell development pathways, but also emphasizes the plasticity and adaptability of the immune system to environmental cues. At the heart of Professor Golub’s scientific inquiry is her commitment to exploring how inflammation affects the development, fate and function of ILC. Her team’s current project is exploring the critical role that the ILC population plays in a range of pathology, including non-alcoholic steatohepatitis.
After graduating from the Great Ekol of the Engineering Agriculture Christian Section, Dr. Elsa Bourayou Decided to engage in research and received his PhD in 2019 under the supervision of Pr rachel Golub, which is located in the laboratory of Pr ana cumano. Her work focuses on natural killer cells and their effects on non-alcoholic steatohepatitis (NASH). More specifically, she is interested in the impact that the pathological environment can have on NK cell development and maturation and how this can further affect the development of the disease. Dr. Bourayou’s future research will focus on the study of immune cell responses during cancer.
