beta 2-Adrenoreceptors of regulatory lymphocytes are essential for vagal neuromodulation of the innate immune system

Article

关键词: CHOLINERGIC ANTIINFLAMMATORY PATHWAY;    TUMOR-NECROSIS-FACTOR;    NICOTINIC ACETYLCHOLINE-RECEPTOR;    SEPTIC SHOCK;    VAGUS NERVE;    HOST RESPONSE;    SEVERE SEPSIS;    PROTEIN;    STIMULATION;    MODULATION;   

DOI  :  10.1096/fj.11-191007

来源: SCIE

【 摘 要 】

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 beta 2-adrenoceptors of splenic regulatory lymphocytes to control systemic inflammation. Vagus nerve stimulation fails to control serum TNF levels in either beta 2-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 beta 2-agonists to control inflammation in both beta 2-knockout and nude mice. beta 2-Agonists inhibit cytokine production in splenocytes (IC50 similar to 1 mu M) and prevent systemic inflammation in wild-type but not in beta 2-knockout mice. beta 2-Agonists rescue wild-type mice from established polymicrobial peritonitis in a clinically relevant time frame. Regulatory lymphocytes reestablish the anti-inflammatory potential of beta 2-agonists to control systemic inflammation, organ damage, and lethal endotoxic shock in beta 2-knockout mice. These results indicate that beta 2-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. Vida, G., Pena, G., Kanashiro, A., del Rocio Thompson-Bonilla, M., Palange, D., Deitch, E. A., Ulloa, L. beta 2-Adrenoreceptors of regulatory lymphocytes are essential for vagal neuromodulation of the innate immune system. FASEB J. 25, 4476-4485 (2011). www.fasebj.org

【 授权许可】

Free