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 Gustafsson; Diane Capen; Dennis Brown; John M. Higgins; David T. Scadden; Peter Libby; Filip K. Swirski; Kamila Naxerova; Matthias Nahrendorf

doi:10.1038/s41590-022-01165-7

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 journal › Article › peer-review

51 Scopus citations

Abstract

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 language	English
Pages (from-to)	605-618
Number of pages	14
Journal	Nature Immunology
Volume	23
Issue number	4
DOIs	https://doi.org/10.1038/s41590-022-01165-7
State	Published - Apr 2022

Access to Document

10.1038/s41590-022-01165-7

Cite this

Schloss, M. J., Hulsmans, M., Rohde, D., Lee, I. H., Severe, N., Foy, B. H., Pulous, F. E., Zhang, S., Kokkaliaris, K. D., Frodermann, V., Courties, G., Yang, C., Iwamoto, Y., Knudsen, A. S., McAlpine, C. S., Yamazoe, M., Schmidt, S. P., Wojtkiewicz, G. R., Masson, G. S., ... Nahrendorf, M. (2022). B lymphocyte-derived acetylcholine limits steady-state and emergency hematopoiesis. Nature Immunology, 23(4), 605-618. https://doi.org/10.1038/s41590-022-01165-7

@article{5ccb24b2347a4ffba96b2112585b38e5,

title = "B lymphocyte-derived acetylcholine limits steady-state and emergency hematopoiesis",

abstract = "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.",

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

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2022",

month = apr,

doi = "10.1038/s41590-022-01165-7",

language = "English",

volume = "23",

pages = "605--618",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Research",

number = "4",

}

Schloss, MJ, Hulsmans, M, Rohde, D, Lee, IH, Severe, N, Foy, BH, Pulous, FE, Zhang, S, Kokkaliaris, KD, Frodermann, V, Courties, G, Yang, C, Iwamoto, Y, Knudsen, AS, McAlpine, CS, Yamazoe, M, Schmidt, SP, Wojtkiewicz, GR, Masson, GS, Gustafsson, K, Capen, D, Brown, D, Higgins, JM, Scadden, DT, Libby, P, Swirski, FK, Naxerova, K & Nahrendorf, M 2022, 'B lymphocyte-derived acetylcholine limits steady-state and emergency hematopoiesis', Nature Immunology, vol. 23, no. 4, pp. 605-618. https://doi.org/10.1038/s41590-022-01165-7

TY - JOUR

T1 - B lymphocyte-derived acetylcholine limits steady-state and emergency hematopoiesis

AU - Schloss, Maximilian J.

AU - Hulsmans, Maarten

AU - Rohde, David

AU - Lee, I. Hsiu

AU - Severe, Nicolas

AU - Foy, Brody H.

AU - Pulous, Fadi E.

AU - Zhang, Shuang

AU - Kokkaliaris, Konstantinos D.

AU - Frodermann, Vanessa

AU - Courties, Gabriel

AU - Yang, Chongbo

AU - Iwamoto, Yoshiko

AU - Knudsen, Anders Steen

AU - McAlpine, Cameron S.

AU - Yamazoe, Masahiro

AU - Schmidt, Stephen P.

AU - Wojtkiewicz, Gregory R.

AU - Masson, Gustavo Santos

AU - Gustafsson, Karin

AU - Capen, Diane

AU - Brown, Dennis

AU - Higgins, John M.

AU - Scadden, David T.

AU - Libby, Peter

AU - Swirski, Filip K.

AU - Naxerova, Kamila

AU - Nahrendorf, Matthias

PY - 2022/4

Y1 - 2022/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85127260395&partnerID=8YFLogxK

U2 - 10.1038/s41590-022-01165-7

DO - 10.1038/s41590-022-01165-7

M3 - Article

C2 - 35352063

AN - SCOPUS:85127260395

SN - 1529-2908

VL - 23

SP - 605

EP - 618

JO - Nature Immunology

JF - Nature Immunology

IS - 4

ER -

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

Abstract

Access to Document

Fingerprint

Cite this