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β2-Adrenoreceptors of regulatory lymphocytes are essential for vagal neuromodulation of the innate immune system.

Authors
  • Vida, Gergely
  • Peña, Geber
  • Kanashiro, Alexandre
  • Thompson-Bonilla, Maria del Rocio
  • Palange, David
  • Deitch, Edwin A
  • Ulloa, Luis
Type
Published Article
Journal
The FASEB Journal
Publisher
Federation of American Society for Experimental Biology
Publication Date
Dec 01, 2011
Volume
25
Issue
12
Pages
4476–4485
Identifiers
DOI: 10.1096/fj.11-191007
PMID: 21840939
Source
Medline
License
Unknown

Abstract

The nervous system is classically organized into sympathetic and parasympathetic systems acting in opposition to maintain physiological homeostasis. Here, we report that both systems converge in the activation of β2-adrenoceptors of splenic regulatory lymphocytes to control systemic inflammation. Vagus nerve stimulation fails to control serum TNF levels in either β2-knockout or lymphocyte-deficient nude mice. Unlike typical suppressor CD25(+) cells, the transfer of CD4(+)CD25(-) regulatory lymphocytes reestablishes the anti-inflammatory potential of the vagus nerve and β2-agonists to control inflammation in both β2-knockout and nude mice. β2-Agonists inhibit cytokine production in splenocytes (IC(50)≈ 1 μM) and prevent systemic inflammation in wild-type but not in β2-knockout mice. β2-Agonists rescue wild-type mice from established polymicrobial peritonitis in a clinically relevant time frame. Regulatory lymphocytes reestablish the anti-inflammatory potential of β2-agonists to control systemic inflammation, organ damage, and lethal endotoxic shock in β2-knockout mice. These results indicate that β2-adrenoceptors in regulatory lymphocytes are critical for the anti-inflammatory potential of the parasympathetic vagus nerve, and they represent a potential pharmacological target for sepsis.

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