Institut Pasteur, Université Paris Cité, INSERM U1223, Lymphocyte and Immunity Unit, 75015 Paris, France.
Institut Pasteur, Université Paris Cité, INSERM U1223, Lymphocyte and Immunity Unit, 75015 Paris, France; Institut Mondor de Recherche Biomédicale (IMRB), INSERM U955, 94000 Créteil, France.
Cell Rep. 2024 Jan 23;43(1):113676. doi: 10.1016/j.celrep.2024.113676. Epub 2024 Jan 12.
Natural killer (NK) cells are the predominant lymphocyte population in the liver. At the onset of non-alcoholic steatohepatitis (NASH), an accumulation of activated NK cells is observed in the liver in parallel with inflammatory monocyte recruitment and an increased systemic inflammation. Using in vivo and in vitro experiments, we unveil a specific stimulation of NK cell-poiesis during NASH by medullary monocytes that trans-present interleukin-15 (IL-15) and secrete osteopontin, a biomarker for patients with NASH. This cellular dialogue leads to increased survival and maturation of NK precursors that are recruited to the liver, where they dampen the inflammatory monocyte infiltration. The increase in the production of both osteopontin and the IL-15/IL-15Rα complex by bone marrow monocytes is induced by endotoxemia. We propose a tripartite gut-liver-bone marrow axis regulating the immune population dynamics and effector functions during liver inflammation.
自然杀伤 (NK) 细胞是肝脏中主要的淋巴细胞群体。在非酒精性脂肪性肝炎 (NASH) 发病初期，观察到激活的 NK 细胞在肝脏中与炎症性单核细胞募集和全身炎症增加并行积累。通过体内和体外实验，我们揭示了骨髓单核细胞在 NASH 期间对 NK 细胞发生的特异性刺激，其通过转呈白细胞介素 15 (IL-15) 和分泌骨桥蛋白而起作用，后者是 NASH 患者的生物标志物。这种细胞对话导致招募到肝脏的 NK 前体的存活和成熟增加，从而抑制炎症性单核细胞浸润。骨髓单核细胞产生的骨桥蛋白和 IL-15/IL-15Rα 复合物的增加是由内毒素血症诱导的。我们提出了一个三方的肠道-肝脏-骨髓轴，调节肝脏炎症期间免疫群体动态和效应功能。
