Bone marrow monocytes sustain NK cell-poiesis during non-alcoholic steatohepatitis
Elsa Bourayou,
Thibaut Perchet,
Sylvain Meunier,
Hugo Bouvier,
Marie-Pierre Mailhe,
Evie Melanitou,
Ana Cumano,
Rachel Golub
Affiliations
Elsa Bourayou
Institut Pasteur, Université Paris Cité, INSERM U1223, Lymphocyte and Immunity Unit, 75015 Paris, France
Thibaut Perchet
Institut Pasteur, Université Paris Cité, INSERM U1223, Lymphocyte and Immunity Unit, 75015 Paris, France
Sylvain Meunier
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
Hugo Bouvier
Institut Pasteur, Université Paris Cité, INSERM U1223, Lymphocyte and Immunity Unit, 75015 Paris, France
Marie-Pierre Mailhe
Institut Pasteur, Université Paris Cité, INSERM U1223, Lymphocyte and Immunity Unit, 75015 Paris, France
Evie Melanitou
Institut Pasteur, Université Paris Cité, Department of Parasites and Insect Vectors, 75015 Paris, France
Ana Cumano
Institut Pasteur, Université Paris Cité, INSERM U1223, Lymphocyte and Immunity Unit, 75015 Paris, France
Rachel Golub
Institut Pasteur, Université Paris Cité, INSERM U1223, Lymphocyte and Immunity Unit, 75015 Paris, France; Corresponding author
Summary: 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.
