Neuroimmune interactions: dendritic cell modulation by the sympathetic nervous system

Takenaka, Maisa C.; Guereschi, Marcia Grando; Basso, Alexandre Salgado

doi:10.1007/s00281-016-0590-0

Cited by 33 publications

(31 citation statements)

References 104 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1 and 2) in the absence or presence of NE. As reported previously 33 NE potently suppressed TNF-α secretion driven by LPS activation. Flowever, this effect was not exclusive to a TLR4 agonist as NE also suppressed TNF-α secretion from every TLR agonist tested (Fig.…”

Section: Resultssupporting

confidence: 87%

“…NE also indirectly limits the magnitude of CD8 + T cell priming by suppressing cross-presentation in dendritic cells 31 . In macrophages, NE suppresses TLR4-dependent secretion of TNF-α, resulting in reduced levels of inflammation and sepsis in response to LPS 32 , and these effects are also observed in populations of dendritic cells 31,33,34 . One mechanism that has been proposed for NE-mediated suppression of LPS-induced TNF-α secretion involves the adaptor molecule β-arrestin, which is post-translationally regulated by adrenergic signaling and blocks NF κ B activation 35 Flowever, it remains unclear how adrenergic signaling broadly impacts inflammatory pathways and what mechanisms regulate general immune suppression mediated by NE.…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

The β2-adrenergic receptor controls inflammation by driving rapid IL-10 secretion

Ağaç

Estrada

Maples

et al. 2018

Brain, Behavior, and Immunity

157

View full text Add to dashboard Cite

The mammalian nervous system communicates important information about the environment to the immune system, but the underlying mechanisms are largely unknown. Secondary lymphoid organs are highly innervated by sympathetic neurons that secrete norepinephrine (NE) as the primary neurotransmitter. Immune cells express adrenergic receptors, enabling the sympathetic nervous system to directly control immune function. NE is a potent immunosuppressive factor and markedly inhibits TNF-α secretion from innate cells in response to lipopolysaccharide (LPS). In this study, we demonstrate that NE blocks the secretion of a variety of proinflammatory cytokines by rapidly inducing IL-10 secretion from innate cells in response to multiple Toll-like receptor (TLR) signals. NE mediated these effects exclusively through the β2-adrenergic receptor (ADRB2). Consequently, Adrb2 animals were more susceptible to L. monocytogenes infection and to intestinal inflammation in a dextran sodium sulfate (DSS) model of colitis. Further, Adrb2 animals rapidly succumbed to endotoxemia in response to a sub-lethal LPS challenge and exhibited elevated serum levels of TNF-α and reduced IL-10. LPS-mediated lethality in WT animals was rescued by administering a β 2-specific agonist and in Adrb2 animals by exogenous IL-10. These findings reveal a critical role for ADRB2 signaling in controlling inflammation through the rapid induction of IL-10. Our findings provide a fundamental insight into how the sympathetic nervous system controls a critical facet of immune function through ADRB2 signaling.

show abstract

Section: Resultssupporting

confidence: 87%

Section: Introductionmentioning

confidence: 98%

The β2-adrenergic receptor controls inflammation by driving rapid IL-10 secretion

Ağaç

Estrada

Maples

et al. 2018

Brain, Behavior, and Immunity

157

View full text Add to dashboard Cite

show abstract

“…Regarding the dendritic cells, it is well-known that these specialized phagocytes are responsible for bridging innate and adaptive immune responses [49], and that β-stimulation turns DCs to an anti-inflammatory state [50] and triggers T cell differentiation [51]. Indeed, sympathetic stimulation is essential for triggering the recovery phase of an immune response [52,53] in lymph nodes [54], bone marrow cells [55], and gut macrophages [56].…”

Section: Discussionmentioning

confidence: 99%

β-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes

Pires-Lapa

Carvalho-Sousa

Cecon

et al. 2018

IJMS

View full text Add to dashboard Cite

Melatonin (5-methoxy-N-acetylserotonin), the pineal hormone, is also synthesized by immune-competent cells. The pineal hormone signals darkness, while melatonin synthesized on demand by activated macrophages at any hour of the day acts locally, favoring regulatory/tolerant phenotypes. Activation of β-adrenoceptors in pinealocytes is the main route for triggering melatonin synthesis. However, despite the well-known role of β-adrenoceptors in the resolution macrophage phenotype (M2), and the relevance of macrophage synthesized melatonin in facilitating phagocytic activity, there is no information regarding whether activation of β-adrenoceptors would induce melatonin synthesis by monocytes. Here we show that catecholamines stimulate melatonin synthesis in bone marrow-derived dendritic cells and RAW 264.7 macrophages. Activation of β-adrenoceptors promotes the synthesis of melatonin by stimulating cyclic AMP/protein kinase A (PKA) pathway and by activating the nuclear translocation of NF-κB. Considering the great number of macrophages around sympathetic nerve terminals, and the relevance of this system for maintaining macrophages in stages compatible to low-grade inflammation, our data open the possibility that extra-pineal melatonin acts as an autocrine/paracrine signal in macrophages under resolution or tolerant phenotypes.

show abstract

“…Potentially as a part of the fight-and-flight reaction that need to ensure survival of the organism, the sympathetic nervous system initially has a pro-inflammatory function (19). In long term, the sympathetic nervous system rather suppresses inflammation via β-adrenergic receptors expressed on Neutrophils, Macrophages, innate lymphoid cells (ILCs) and other immune cells (20)(21)(22)(23)(24)(25). The exact response of catecholamines, however, is also context-dependent for example on environment and local challenges, co-stimulatory factors and activation levels of cells (19).…”

Section: Extrinsic Innervationmentioning

confidence: 99%

Neuro-Immune Circuits Regulate Immune Responses in Tissues and Organ Homeostasis

2020

View full text Add to dashboard Cite

The dense innervation of the gastro-intestinal tract with neuronal networks, which are in close proximity to immune cells, implies a pivotal role of neurons in modulating immune functions. Neurons have the ability to directly sense danger signals, adapt immune effector functions and integrate these signals to maintain tissue integrity and host defense strategies. The expression pattern of a large set of immune cells in the intestine characterized by receptors for neurotransmitters and neuropeptides suggest a tight neuronal hierarchical control of immune functions in order to systemically control immune reactions. Compelling evidence implies that targeting neuro-immune interactions is a promising strategy to dampen immune responses in autoimmune diseases such as inflammatory bowel diseases or rheumatoid arthritis. In fact, electric stimulation of vagal fibers has been shown to be an extremely effective treatment strategy against overwhelming immune reactions, even after exhausted conventional treatment strategies. Such findings argue that the nervous system is underestimated coordinator of immune reactions and underline the importance of neuro-immune crosstalk for body homeostasis. Herein, we review neuro-immune interactions with a special focus on disease pathogenesis throughout the gastro-intestinal tract.

show abstract

Neuroimmune interactions: dendritic cell modulation by the sympathetic nervous system

Cited by 33 publications

References 104 publications

The β2-adrenergic receptor controls inflammation by driving rapid IL-10 secretion

The β2-adrenergic receptor controls inflammation by driving rapid IL-10 secretion

β-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes

Neuro-Immune Circuits Regulate Immune Responses in Tissues and Organ Homeostasis

Contact Info

Product

Resources

About