Spleen fibroblastic reticular cell-derived acetylcholine promotes lipid metabolism to drive autoreactive B cell responses

Zeng, Qin; Wang, Shuyi; Li, Mengyuan; Wang, Shuang; Guo, Chaohuan; Ruan, Xinyuan; Watanabe, Ryu; Lai, Yimei; Huang, Yuefang; Yin, Xiaoyu; Zhang, Chuanzhao; Chen, Binfeng; Yang, Niansheng; Zhang, Hui

doi:10.1016/j.cmet.2023.03.010

Cited by 19 publications

(4 citation statements)

References 75 publications

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“…23 Acetylcholine is also produced by FRCs in the spleen of systemic lupus erythematosus-prone mice where acting on B cells expressing both muscarinic and nicotinic receptors, promote autoreactive B-cell response by enhancing lipid metabolism and B-cell differentiation. 22 On another note, our studies demonstrated that hypertensive stimuli recruit a cholinergic-sympathetic modulation of the spleen through a different axis. 16,18 At the anatomic level, the connection between the 2 arms of the ANS, the noradrenergic and the cholinergic fibers, is established in the celiac ganglion.…”

Section: Sensory and Noradrenergic Fibers Innervating The Spleenmentioning

confidence: 68%

“…20 Neurons originating in the celiac ganglion and innervating the spleen also release neuropeptide Y that dampen local splenic inflammatory response after LPS (lipopolysaccharide) stimulation and are able to restore immune balance in autoimmune diseases. 21 Although the spleen is not directly innervated by cholinergic fibers, acetylcholine was found in tissue homogenates, and recent work demonstrated that it is locally produced by FRCs 22 and immune cells 23 and is able to modulate lipid metabolism and immune cell differentiation and activation. In particular, it was shown that, upon splenic noradrenergic discharge, a specific subset of CD4 T cells, expressing the enzyme ChAT (choline acetyltransferase), release acetylcholine, which in turn modulates the activity of macrophages.…”

Section: Sensory and Noradrenergic Fibers Innervating The Spleenmentioning

confidence: 99%

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Brain-Splenic Immune System Interactions in Hypertension: Cellular and Molecular Mechanisms

Perrotta,

Carnevale

2024

ATVB

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Hypertension represents a major worldwide cause of death and disability, and it is becoming increasingly clear that available therapies are not sufficient to reduce the risk of major cardiovascular events. Various mechanisms contribute to blood pressure increase: neurohormonal activation, autonomic nervous system imbalance, and immune activation. Of note, the brain is an important regulator of blood pressure levels; it recognizes the peripheral perturbation and organizes a reflex response by modulating immune system and hormonal release to attempt at restoring the homeostasis. The connection between the brain and peripheral organs is mediated by the autonomic nervous system, which also modulates immune and inflammatory responses. Interestingly, an increased autonomic nervous system activity has been correlated with an altered immune response in cardiovascular diseases. The spleen is the largest immune organ exerting a potent influence on the cardiovascular system during disease and is characterized by a dense noradrenergic innervation. Taken together, these aspects led to hypothesize a key role of neuroimmune mechanisms in the onset and progression of hypertension. This review discusses how the nervous and splenic immune systems interact and how the mechanisms underlying the neuroimmune cross talk influence the disease progression.

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Section: Sensory and Noradrenergic Fibers Innervating The Spleenmentioning

confidence: 68%

Section: Sensory and Noradrenergic Fibers Innervating The Spleenmentioning

confidence: 99%

Brain-Splenic Immune System Interactions in Hypertension: Cellular and Molecular Mechanisms

Perrotta,

Carnevale

2024

ATVB

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“…Further support for the role of adrenergic receptors in modulation of immunity comes from studies of CD86, a transmembrane glycoprotein expressed at low levels primarily on antigen-presenting cells, including B cells. Through binding to CD28 and CTLA-4 expressed on CD4+4 T cells, CD86 acts as a costimulatory molecule that can increase or decrease T cell activation signaling, respectively [ 33 ]. CD86 expression on resting B cells can be upregulated in response to engagement with CD40, LPS, IL-4 receptor, or the B cell receptor.…”

Section: Adrenergic Modulation Of the Adaptive Immune Responsementioning

confidence: 99%

Pharmacological and Electroceutical Targeting of the Cholinergic Anti-Inflammatory Pathway in Autoimmune Diseases

Zouali

2023

Pharmaceuticals

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Continuous dialogue between the immune system and the brain plays a key homeostatic role in various immune responses to environmental cues. Several functions are under the control of the vagus nerve-based inflammatory reflex, a physiological mechanism through which nerve signals regulate immune functions. In the cholinergic anti-inflammatory pathway, the vagus nerve, its pivotal neurotransmitter acetylcholine, together with the corresponding receptors play a key role in modulating the immune response of mammals. Through communications of peripheral nerves with immune cells, it modulates proliferation and differentiation activities of various immune cell subsets. As a result, this pathway represents a potential target for treating autoimmune diseases characterized by overt inflammation and a decrease in vagal tone. Consistently, converging observations made in both animal models and clinical trials revealed that targeting the cholinergic anti-inflammatory pathway using pharmacologic approaches can provide beneficial effects. In parallel, bioelectronic medicine has recently emerged as an alternative approach to managing systemic inflammation. In several studies, nerve electrostimulation was reported to be clinically relevant in reducing chronic inflammation in autoimmune diseases, including rheumatoid arthritis and diabetes. In the future, these new approaches could represent a major therapeutic strategy for autoimmune and inflammatory diseases.

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“…Researchers have identified a novel function of acetylcholine produced by spleen fibroblastic reticular cells (FRCs) in driving autoimmune responses in systemic lupus erythematosus (SLE), according to a new study published in Cell Metabolism recently 1 . The study links the neurotransmitter acetylcholine to the lipid metabolism of autoreactive B cells in the pathogenesis of SLE.…”

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confidence: 99%

Acetylcholine promotes autoreactive B cell response

Li¹

2023

Rheumatology & Autoimmunity

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Spleen fibroblastic reticular cell-derived acetylcholine promotes lipid metabolism to drive autoreactive B cell responses

Cited by 19 publications

References 75 publications

Brain-Splenic Immune System Interactions in Hypertension: Cellular and Molecular Mechanisms

Brain-Splenic Immune System Interactions in Hypertension: Cellular and Molecular Mechanisms

Pharmacological and Electroceutical Targeting of the Cholinergic Anti-Inflammatory Pathway in Autoimmune Diseases

Acetylcholine promotes autoreactive B cell response

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