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Control of lymphocyte egress from lymph nodes through β2-adrenergic receptors.

ABSTRACT: Lymphocyte recirculation through secondary lymphoid organs is essential for immunosurveillance and lymphocyte effector functions. Here, we show that signals through β2-adrenergic receptors (β2ARs) expressed on lymphocytes are involved in the control of lymphocyte dynamics by altering the responsiveness of chemoattractant receptors. Agonist stimulation of lymphocyte β2ARs inhibited egress of lymphocytes from lymph nodes (LNs) and rapidly produced lymphopenia in mice. Physiological inputs from adrenergic nerves contributed to retention of lymphocytes within LNs and homeostasis of their distribution among lymphoid tissues. β2ARs physically interacted with CCR7 and CXCR4, chemokine receptors promoting lymphocyte retention in LNs. Activation of β2ARs enhanced retention-promoting signals through CCR7 and CXCR4, and consequently inhibited lymphocyte egress from LNs. In models of T cell-mediated inflammatory diseases, β2AR-mediated signals inhibited LN egress of antigen-primed T cells and reduced their recruitment into peripheral tissues. Thus, this study reveals a novel mechanism for controlling lymphocyte trafficking and provides additional insights into immune regulation by the nervous system.

SUBMITTER: Nakai A

PROVIDER: S-EPMC4267238 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Control of lymphocyte egress from lymph nodes through β2-adrenergic receptors.

Nakai Akiko A Hayano Yuki Y Furuta Fumika F Noda Masaki M Suzuki Kazuhiro K

The Journal of experimental medicine 20141124 13

Lymphocyte recirculation through secondary lymphoid organs is essential for immunosurveillance and lymphocyte effector functions. Here, we show that signals through β2-adrenergic receptors (β2ARs) expressed on lymphocytes are involved in the control of lymphocyte dynamics by altering the responsiveness of chemoattractant receptors. Agonist stimulation of lymphocyte β2ARs inhibited egress of lymphocytes from lymph nodes (LNs) and rapidly produced lymphopenia in mice. Physiological inputs from adr ...[more]

PMID: 25422496

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Project description:IntroductionDexmedetomidine (DEX) is primarily utilized for sedation in the context of general anesthesia or intensive care. However, the exact regulatory mechanism by which DEX affects cytokines remains unclear. This study aims to investigate the underlying mechanism by which DEX inhibits proinflammatory factors through activation of the β2 adrenergic receptor (β2 AR).MethodsThe inflammatory cell model of human mononuclear macrophage (THP-1) cells induced by lipopolysaccharide (LPS) was established to study the effect of DEX on the expression of cell-related inflammatory factors. ADRA2A gene knockout THP-1 cells (THP-1KO ) were constructed by CRISPR technology, and the effect of DEX on the expression of inflammatory factors of THP-1KO cells was detected. The target sites of DEX on β2 AR were screened by molecular docking. Reversion experiments were performed using ADRB2-siRNA. Western blot was used to detect the activation of β2 AR/PKA/CREB pathway and NF-κB, and ELISA was used to detect the release level of inflammatory factors.ResultsThe results demonstrated a significant reduction in the expression levels of MCP-1, interleukin-06, and IL-8 in both THP-1 and THP-1KO cells when induced by LPS following treatment with DEX. Additionally, DEX treatment led to an increase in IL-10 expression. Immunofluorescence analysis revealed an upregulation of β2 AR expression after DEX treatment. Western blot results indicated that DEX notably enhanced the activation of the β2 AR and PKA/CREB pathways, while concurrently suppressing the activation of NF-κB. Notably, the use of ADRB2 siRNA reversed the effects of DEX treatment and promoted the release of inflammatory cytokines.ConclusionDEX initiates the activation of the PKA/CREB pathway through the activation of β2 AR. Simultaneously, it exerts an inhibitory effect on the activation of NF-κB, consequently reducing the transcription of proinflammatory factors while increasing the transcription of anti-inflammatory factors.

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Control of lymphocyte egress from lymph nodes through β2-adrenergic receptors.

Publications

Control of lymphocyte egress from lymph nodes through β2-adrenergic receptors.

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