TY - JOUR T1 - Mature B cells and mesenchymal stem cells control emergency myelopoiesis JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202301924 VL - 6 IS - 4 SP - e202301924 AU - Vivian Y Lim AU - Xing Feng AU - Runfeng Miao AU - Sandra Zehentmeier AU - Nathan Ewing-Crystal AU - Moonyoung Lee AU - Alexei V Tumanov AU - Ji Eun Oh AU - Akiko Iwasaki AU - Andrew Wang AU - Jungmin Choi AU - João P Pereira Y1 - 2023/04/01 UR - https://www.life-science-alliance.org/content/6/4/e202301924.abstract N2 - Systemic inflammation halts lymphopoiesis and prioritizes myeloid cell production. How blood cell production switches from homeostasis to emergency myelopoiesis is incompletely understood. Here, we show that lymphotoxin-β receptor (LTβR) signaling in combination with TNF and IL-1 receptor signaling in bone marrow mesenchymal stem cells (MSCs) down-regulates Il7 expression to shut down lymphopoiesis during systemic inflammation. LTβR signaling in MSCs also promoted CCL2 production during systemic inflammation. Pharmacological or genetic blocking of LTβR signaling in MSCs partially enabled lymphopoiesis and reduced monocyte numbers in the spleen during systemic inflammation, which correlated with reduced survival during systemic bacterial and viral infections. Interestingly, lymphotoxin-α1β2 delivered by B-lineage cells, and specifically by mature B cells, contributed to promote Il7 down-regulation and reduce MSC lymphopoietic activity. Our studies revealed an unexpected role of LTβR signaling in MSCs and identified recirculating mature B cells as an important regulator of emergency myelopoiesis. ER -