title: 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.
authors.affiliation: WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Nakai
authors.affiliation: WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hayano
authors.affiliation: WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Fumika
authors.initials: F
authors.lastname: Furuta
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Global Center of Excellence Program, and Department of Maxillofacial Orthognathics, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Noda
authors.affiliation: WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan ksuzuki@ifrec.osaka-u.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008231:Lymphopenia / Q000276:immunology / Q000473:pathology; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D054400:Receptors, CCR7 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
chemical_list: D000941:Antigens; D018343:Receptors, Adrenergic, beta-2; D054400:Receptors, CCR7; D019718:Receptors, CXCR4