B lymphocyte-derived acetylcholine limits steady-state and emergency hematopoiesis

Maximilian J. Schloss, Maarten Hulsmans, David Rohde, I. Hsiu Lee, Nicolas Severe, Brody H. Foy, Fadi E. Pulous, Shuang Zhang, Konstantinos D. Kokkaliaris, Vanessa Frodermann, Gabriel Courties, Chongbo Yang, Yoshiko Iwamoto, Anders Steen Knudsen, Cameron S. McAlpine, Masahiro Yamazoe, Stephen P. Schmidt, Gregory R. Wojtkiewicz, Gustavo Santos Masson, Karin GustafssonDiane Capen, Dennis Brown, John M. Higgins, David T. Scadden, Peter Libby, Filip K. Swirski, Kamila Naxerova, Matthias Nahrendorf

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Autonomic nerves control organ function through the sympathetic and parasympathetic branches, which have opposite effects. In the bone marrow, sympathetic (adrenergic) nerves promote hematopoiesis; however, how parasympathetic (cholinergic) signals modulate hematopoiesis is unclear. Here, we show that B lymphocytes are an important source of acetylcholine, a neurotransmitter of the parasympathetic nervous system, which reduced hematopoiesis. Single-cell RNA sequencing identified nine clusters of cells that expressed the cholinergic α7 nicotinic receptor (Chrna7) in the bone marrow stem cell niche, including endothelial and mesenchymal stromal cells (MSCs). Deletion of B cell-derived acetylcholine resulted in the differential expression of various genes, including Cxcl12 in leptin receptor+ (LepR+) stromal cells. Pharmacologic inhibition of acetylcholine signaling increased the systemic supply of inflammatory myeloid cells in mice and humans with cardiovascular disease.

Original languageEnglish
Pages (from-to)605-618
Number of pages14
JournalNature Immunology
Issue number4
StatePublished - Apr 2022


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