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

Nakai, Akiko, Hayano, Yuki, Furuta, Fumika, Noda, Masaki, Suzuki, Kazuhiro·2014·Journal of Experimental Medicine
DOI 10.1084/jem.20141132
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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.

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Research works printed but not linked: 44

  1. Andersson, 2012, Reflex principles of immunological homeostasis, Annu. Rev. Immunol., 30, 313, 10.1146/annurev-immunol-020711-075015 · DOI · Paper page
  2. Arima, 2012, Regional neural activation defines a gateway for autoreactive T cells to cross the blood-brain barrier, Cell., 148, 447, 10.1016/j.cell.2012.01.022 · DOI · Paper page
  3. Arnon, 2011, GRK2-dependent S1PR1 desensitization is required for lymphocytes to overcome their attraction to blood, Science., 333, 1898, 10.1126/science.1208248 · DOI · Paper page
  4. Barnden, 1998, Defective TCR expression in transgenic mice constructed using cDNA-based alpha- and beta-chain genes under the control of heterologous regulatory elements, Immunol. Cell Biol., 76, 34, 10.1046/j.1440-1711.1998.00709.x · DOI · Paper page
  5. Bellinger, 2008, Sympathetic modulation of immunity: relevance to disease, Cell. Immunol., 252, 27, 10.1016/j.cellimm.2007.09.005 · DOI · Paper page
  6. Brinkmann, 2010, Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis, Nat. Rev. Drug Discov., 9, 883, 10.1038/nrd3248 · DOI · Paper page
  7. Chelmicka-Schorr, 1989, The beta-adrenergic agonist isoproterenol suppresses experimental allergic encephalomyelitis in Lewis rats, J. Neuroimmunol., 25, 203, 10.1016/0165-5728(89)90138-0 · DOI
  8. Curtis, 2014, Circadian clock proteins and immunity, Immunity., 40, 178, 10.1016/j.immuni.2014.02.002 · DOI · Paper page
  9. Cyster, 2012, Sphingosine-1-phosphate and lymphocyte egress from lymphoid organs, Annu. Rev. Immunol., 30, 69, 10.1146/annurev-immunol-020711-075011 · DOI · Paper page
  10. Elenkov, 2000, The sympathetic nerve—an integrative interface between two supersystems: the brain and the immune system, Pharmacol. Rev., 52, 595, 10.1016/S0031-6997(24)01470-4 · DOI · Paper page
  11. Förster, 1999, CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs, Cell., 99, 23, 10.1016/S0092-8674(00)80059-8 · DOI · Paper page
  12. Grebe, 2009, Sympathetic nervous system control of anti-influenza CD8+ T cell responses, Proc. Natl. Acad. Sci. USA., 106, 5300, 10.1073/pnas.0808851106 · DOI
  13. Grebe, 2010, Cutting edge: Sympathetic nervous system increases proinflammatory cytokines and exacerbates influenza A virus pathogenesis, J. Immunol., 184, 540, 10.4049/jimmunol.0903395 · DOI · Paper page
  14. Grigorova, 2009, Cortical sinus probing, S1P1-dependent entry and flow-based capture of egressing T cells, Nat. Immunol., 10, 58, 10.1038/ni.1682 · DOI · Paper page
  15. Hanyu, 2012, Anabolic action of parathyroid hormone regulated by the β2-adrenergic receptor, Proc. Natl. Acad. Sci. USA., 109, 7433, 10.1073/pnas.1109036109 · DOI
  16. Hervé, 2013, β2-Adrenoreceptor agonist inhibits antigen cross-presentation by dendritic cells, J. Immunol., 190, 3163, 10.4049/jimmunol.1201391 · DOI
  17. Hu, 2012, Salmeterol attenuates the inflammatory response in asthma and decreases the pro-inflammatory cytokine secretion of dendritic cells, Cell. Mol. Immunol., 9, 267, 10.1038/cmi.2011.56 · DOI
  18. Kwan, 2004, CCR7 directs the migration of thymocytes into the thymic medulla, J. Immunol., 172, 3999, 10.4049/jimmunol.172.7.3999 · DOI · Paper page
  19. Lo, 2005, Cyclical modulation of sphingosine-1-phosphate receptor 1 surface expression during lymphocyte recirculation and relationship to lymphoid organ transit, J. Exp. Med., 201, 291, 10.1084/jem.20041509 · DOI · Paper page
  20. Ma, 1999, The chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within the bone marrow microenvironment, Immunity., 10, 463, 10.1016/S1074-7613(00)80046-1 · DOI · Paper page
  21. Mandala, 2002, Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists, Science., 296, 346, 10.1126/science.1070238 · DOI · Paper page
  22. McElroy, 1988, Discriminative stimulus properties of clenbuterol: evidence for beta adrenergic involvement, J. Pharmacol. Exp. Ther., 245, 155, 10.1016/S0022-3565(25)22283-2 · DOI
  23. Méndez-Ferrer, 2008, Haematopoietic stem cell release is regulated by circadian oscillations, Nature., 452, 442, 10.1038/nature06685 · DOI · Paper page
  24. Milligan, 2009, G protein-coupled receptor hetero-dimerization: contribution to pharmacology and function, Br. J. Pharmacol., 158, 5, 10.1111/j.1476-5381.2009.00169.x · DOI · Paper page
  25. Moon, 2007, Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude, Immunity., 27, 203, 10.1016/j.immuni.2007.07.007 · DOI · Paper page
  26. Ngo, 1998, Epstein-Barr virus-induced molecule 1 ligand chemokine is expressed by dendritic cells in lymphoid tissues and strongly attracts naive T cells and activated B cells, J. Exp. Med., 188, 181, 10.1084/jem.188.1.181 · DOI · Paper page
  27. Nguyen, 2013, Circadian gene Bmal1 regulates diurnal oscillations of Ly6C(hi) inflammatory monocytes, Science., 341, 1483, 10.1126/science.1240636 · DOI · Paper page
  28. Nijhuis, 2014, Adrenergic β2 receptor activation stimulates anti-inflammatory properties of dendritic cells in vitro, PLoS ONE., 9, e85086, 10.1371/journal.pone.0085086 · DOI
  29. Okada, 2002, Chemokine requirements for B cell entry to lymph nodes and Peyer’s patches, J. Exp. Med., 196, 65, 10.1084/jem.20020201 · DOI · Paper page
  30. Pham, 2010, Lymphatic endothelial cell sphingosine kinase activity is required for lymphocyte egress and lymphatic patterning, J. Exp. Med., 207, 17, 10.1084/jem.20091619 · DOI · Paper page
  31. Pham, 2008, S1P1 receptor signaling overrides retention mediated by G alpha i-coupled receptors to promote T cell egress, Immunity., 28, 122, 10.1016/j.immuni.2007.11.017 · DOI · Paper page
  32. Prezeau, 2010, Functional crosstalk between GPCRs: with or without oligomerization, Curr. Opin. Pharmacol., 10, 6, 10.1016/j.coph.2009.10.009 · DOI
  33. Rosen, 2005, Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network, Nat. Rev. Immunol., 5, 560, 10.1038/nri1650 · DOI · Paper page
  34. Sanders, 2012, The beta2-adrenergic receptor on T and B lymphocytes: do we understand it yet?, Brain Behav. Immun., 26, 195, 10.1016/j.bbi.2011.08.001 · DOI · Paper page
  35. Scheiermann, 2012, Adrenergic nerves govern circadian leukocyte recruitment to tissues, Immunity., 37, 290, 10.1016/j.immuni.2012.05.021 · DOI · Paper page
  36. Schmidt, 2013, CXCR4 promotes B cell egress from Peyer’s patches, J. Exp. Med., 210, 1099, 10.1084/jem.20122574 · DOI
  37. Schwab, 2007, Finding a way out: lymphocyte egress from lymphoid organs, Nat. Immunol., 8, 1295, 10.1038/ni1545 · DOI · Paper page
  38. Silver, 2012, The circadian clock controls toll-like receptor 9-mediated innate and adaptive immunity, Immunity., 36, 251, 10.1016/j.immuni.2011.12.017 · DOI · Paper page
  39. Sinha, 2009, B lymphocytes exit lymph nodes through cortical lymphatic sinusoids by a mechanism independent of sphingosine-1-phosphate-mediated chemotaxis, Immunity., 30, 434, 10.1016/j.immuni.2008.12.018 · DOI
  40. Smith, 1998, The pharmacokinetics, metabolism, and tissue residues of beta-adrenergic agonists in livestock, J. Anim. Sci., 76, 173, 10.2527/1998.761173x · DOI · Paper page
  41. Steinman, 2014, Immunology of relapse and remission in multiple sclerosis, Annu. Rev. Immunol., 32, 257, 10.1146/annurev-immunol-032713-120227 · DOI · Paper page
  42. von Andrian, 2003, Homing and cellular traffic in lymph nodes, Nat. Rev. Immunol., 3, 867, 10.1038/nri1222 · DOI · Paper page
  43. Wiegmann, 1995, Beta-adrenergic agonists suppress chronic/relapsing experimental allergic encephalomyelitis (CREAE) in Lewis rats, J. Neuroimmunol., 56, 201, 10.1016/0165-5728(94)00153-F · DOI
  44. Wong, 2011, Functional innervation of hepatic iNKT cells is immunosuppressive following stroke, Science., 334, 101, 10.1126/science.1210301 · DOI · Paper page

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Metadata

Authors
Nakai, A., Hayano, Y., Furuta, F., Noda, M., & Suzuki, K.
Venue
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2014-11-24
Volume
211
Issue
13
Pages
2583-2598
ISSN
  • 1540-9538
  • 0022-1007
DOI
10.1084/jem.20141132
Cited by
290
References
6
Language
en

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Nakai, A., Hayano, Y., Furuta, F., Noda, M., & Suzuki, K. (2014). Control of lymphocyte egress from lymph nodes through β2-adrenergic receptors. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20141132

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