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

Didem Ağaç, Leonardo D. Estrada, Robert Maples, Lora V. Hooper, J. David Farrar

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalBrain, Behavior, and Immunity
DOIs
StateAccepted/In press - Jan 1 2018

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Interleukin-10
Adrenergic Receptors
Norepinephrine
Inflammation
Lipopolysaccharides
Sympathetic Nervous System
Dextran Sulfate
Endotoxemia
Toll-Like Receptors
Colitis
Immunosuppressive Agents
Nervous System
Neurotransmitter Agents
Immune System
Cytokines
Neurons
Infection
Serum

Keywords

  • Adrenergic receptor
  • Inflammation
  • Interleukin-10
  • Macrophage
  • Norepinephrine
  • Sepsis

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Cite this

The β2-adrenergic receptor controls inflammation by driving rapid IL-10 secretion. / Ağaç, Didem; Estrada, Leonardo D.; Maples, Robert; Hooper, Lora V.; Farrar, J. David.

In: Brain, Behavior, and Immunity, 01.01.2018.

Research output: Contribution to journalArticle

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