The sympathetic nervous system modulates CD4+Foxp3+ regulatory T cells via noradrenaline-dependent apoptosis in a murine model of lymphoproliferative disease

Brain, Behavior, and Immunity

Volumn 38, Issue , 2014, Pages 100-110

  Wirth, Timo ^a,b   Westendorf, Astrid M ^a   Bloemker, Dominique ^a   Wildmann, Johannes ^b   Engler, Harald ^a   Mollerus, Sina ^a   Wadwa, Munisch ^a   Schäfer, Martin K H ^b   Schedlowski, Manfred ^a   del Rey, Adriana ^b  

^a UNIVERSITY HOSPITAL ESSEN   (Germany)

^b PHILIPPS UNIVERSITY MARBURG   (Germany)

Author keywords

Apoptosis; Autoimmune lymphoproliferative syndrome; Foxp3; Noradrenaline; Sympathetic nervous system; Systemic lupus erythematosus; Treg

Indexed keywords

BETA 2 ADRENERGIC RECEPTOR; MESSENGER RNA; NORADRENALIN; OXIDOPAMINE; TRANSCRIPTION FACTOR FOXP3; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, MOUSE;

ADRENERGIC SYSTEM; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; FEMALE; IMMUNOMODULATION; LYMPH NODE; LYMPHOPROLIFERATIVE DISEASE; MALE; MOUSE; NERVE FIBER; NEUROMODULATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; REGULATORY T LYMPHOCYTE; SPLEEN; SYMPATHECTOMY; SYMPATHETIC INNERVATION; SYMPATHETIC NERVE; THYMUS; ANIMAL CELL; ANIMAL TISSUE; CD4+ FOXP3+ REGULATORY T LYMPHOCYTE; IN VITRO STUDY; ANIMAL; C57BL MOUSE; DISEASE MODEL; IMMUNOLOGY; INNERVATION; METABOLISM;

ANIMALS; APOPTOSIS; DISEASE MODELS, ANIMAL; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; LYMPHOPROLIFERATIVE DISORDERS; MALE; MICE; MICE, INBRED C57BL; NOREPINEPHRINE; SPLEEN; SYMPATHETIC NERVOUS SYSTEM; T-LYMPHOCYTES, REGULATORY;

EID: 84898548829     PISSN: 08891591     EISSN: 10902139     Source Type: Journal    
DOI: 10.1016/j.bbi.2014.01.007     Document Type: Article

References (41)

1. Abe J., Ueha S., Suzuki J., Tokano Y., Matsushima K., Ishikawa S. Increased Foxp3(+) CD4(+) regulatory T cells with intact suppressive activity but altered cellular localization in murine lupus. Am. J. Pathol. 2008, 173:1682-1692.
2. Aswad F., Kawamura H., Dennert G. High sensitivity of CD4+CD25+ regulatory T cells to extracellular metabolites nicotinamide adenine dinucleotide and ATP: a role for P2X7 receptors. J. Immunol. 2005, 175:3075-3083.
3. Banz A., Pontoux C., Papiernik M. Modulation of Fas-dependent apoptosis: a dynamic process controlling both the persistence and death of CD4 regulatory T cells and effector T cells. J. Immunol. 2002, 169:750-757.
4. Baratelli F., Lin Y., Zhu L., Yang S.C., Heuze-Vourc'h N., Zeng G., Reckamp K., Dohadwala M., Sharma S., Dubinett S.M. Prostaglandin E2 induces FOXP3 gene expression and T regulatory cell function in human CD4+ T cells. J. Immunol. 2005, 175:1483-1490.
5. Bhowmick S., Singh A., Flavell R.A., Clark R.B., O'Rourke J., Cone R.E. The sympathetic nervous system modulates CD4(+)FoxP3(+) regulatory T cells via a TGF-beta-dependent mechanism. J. Leukoc. Biol. 2009, 86:1275-1283.
6. Chen X., Murakami T., Oppenheim J.J., Howard O.M. Differential response of murine CD4+CD25+ and CD4+CD25- T cells to dexamethasone-induced cell death. Eur. J. Immunol. 2004, 34:859-869.
7. Chen X., Oppenheim J.J., Winkler-Pickett R.T., Ortaldo J.R., Howard O.M. Glucocorticoid amplifies IL-2-dependent expansion of functional FoxP3(+)CD4(+)CD25(+) T regulatory cells in vivo and enhances their capacity to suppress EAE. Eur. J. Immunol. 2006, 36:2139-2149.
8. Crellin N.K., Garcia R.V., Hadisfar O., Allan S.E., Steiner T.S., Levings M.K. Human CD4+ T cells express TLR5 and its ligand flagellin enhances the suppressive capacity and expression of FOXP3 in CD4+CD25+ T regulatory cells. J. Immunol. 2005, 175:8051-8059.
9. del Rey A., Besedovsky H.O. Sympathetic nervous system-immune interactions in autoimmune lymphoproliferative diseases. Neuroimmunomodulation 2008, 15:29-36.
10. del Rey A., Kabiersch A., Petzoldt S., Besedovsky H.O. Sympathetic abnormalities during autoimmune processes: potential relevance of noradrenaline-induced apoptosis. Ann. N. Y. Acad. Sci. 2003, 992:158-167.
11. del Rey A., Roggero E., Kabiersch A., Schafer M., Besedovsky H.O. The role of noradrenergic nerves in the development of the lymphoproliferative disease in Fas-deficient, lpr/lpr mice. J. Immunol. 2006, 176:7079-7086.
12. Ding Y., Xu J., Bromberg J.S. Regulatory T cell migration during an immune response. Trends Immunol. 2012, 33:174-180.
13. Elenkov I.J., Wilder R.L., Chrousos G.P., Vizi E.S. The sympathetic nerve - an integrative interface between two supersystems: the brain and the immune system. Pharmacol. Rev. 2000, 52:595-638.
14. Felten S.Y., Olschowka J. Noradrenergic sympathetic innervation of the spleen: II. Tyrosine hydroxylase (TH)-positive nerve terminals form synaptic like contacts on lymphocytes in the splenic white pulp. J. Neurosci. Res. 1987, 18:37-48.
15. Gu C., Ma Y.C., Benjamin J., Littman D., Chao M.V., Huang X.Y. Apoptotic signaling through the beta-adrenergic receptor. a new Gs effector pathway. J. Biol. Chem. 2000, 275:20726-20733.
16. Guereschi M.G., Araujo L.P., Maricato J.T., Takenaka M.C., Nascimento V.M., Vivanco B.C., Reis V.O., Keller A.C., Brum P.C., Basso A.S. Beta2-adrenergic receptor signaling in CD4(+) Foxp3(+) regulatory T cells enhances their suppressive function in a PKA-dependent manner. Eur. J. Immunol. 2013, 43:1001-1012.
17. Hondowicz B.D., Fields M.L., Nish S.A., Larkin J., Caton A.J., Erikson J. Autoantibody production in lpr/lpr gld/gld mice reflects accumulation of CD4+ effector cells that are resistant to regulatory T cell activity. J. Autoimmun. 2008, 31:98-109.
18. Hori S., Nomura T., Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003, 299:1057-1061.
19. Karagiannidis C., Akdis M., Holopainen P., Woolley N.J., Hense G., Ruckert B., Mantel P.Y., Menz G., Akdis C.A., Blaser K., Schmidt-Weber C.B. Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma. J. Allergy Clin. Immunol. 2004, 114:1425-1433.
20. Kim H.R., Kie J.H., Lim W., Moon B.I., Kim S.C., Seoh J.Y. CD4(+)CD25(+) regulatory T cells from MRL/lpr mice were functionally more active in vitro but did not prevent spontaneous as well as adriamycin-induced nephropathy in vivo. Rheumatology 2012, 51:1357-1367.
21. Kipnis J., Cardon M., Avidan H., Lewitus G.M., Mordechay S., Rolls A., Shani Y., Schwartz M. Dopamine, through the extracellular signal-regulated kinase pathway, downregulates CD4+CD25+ regulatory T-cell activity: implications for neurodegeneration. J. Neurosci. 2004, 24:6133-6143.
22. Kohm A.P., Sanders V.M. Norepinephrine and beta 2-adrenergic receptor stimulation regulate CD4+ T and B lymphocyte function in vitro and in vivo. Pharmacol. Rev. 2001, 53:487-525.
23. Lorton D., Hewitt D., Bellinger D.L., Felten S.Y., Felten D.L. Noradrenergic reinnervation of the rat spleen following chemical sympathectomy with 6-hydroxydopamine: pattern and time course of reinnervation. Brain Behav. Immun. 1990, 4:198-222.
24. Nance D.M., Sanders V.M. Autonomic innervation and regulation of the immune system (1987-2007). Brain Behav. Immun. 2007, 21:736-745.
25. Nguyen V.H., Zeiser R., Dasilva D.L., Chang D.S., Beilhack A., Contag C.H., Negrin R.S. In vivo dynamics of regulatory T-cell trafficking and survival predict effective strategies to control graft-versus-host disease following allogeneic transplantation. Blood 2007, 109:2649-2656.
26. Papiernik M., do Carmo Leite-de-Moraes M., Pontoux C., Joret A.M., Rocha B., Penit C., Dy M. T cell deletion induced by chronic infection with mouse mammary tumor virus spares a CD25-positive, IL-10-producing T cell population with infectious capacity. J. Immunol. 1997, 158:4642-4653.
27. Piccirillo C.A. Regulatory T cells in health and disease. Cytokine 2008, 43:395-401.
28. Prado C., Gómez J., López P., de Paz B., Gutiérrez C., Suárez A. Dexamethasone upregulates FOXP3 expression without increasing regulatory activity. Immunobiology 2011, 216:386-392.
29. Riether C., Kavelaars A., Wirth T., Pacheco-Lopez G., Doenlen R., Willemen H., Heijnen C.J., Schedlowski M., Engler H. Stimulation of beta(2)-adrenergic receptors inhibits calcineurin activity in CD4(+) T cells via PKA-AKAP interaction. Brain Behav. Immun. 2011, 25:59-66.
30. Roncador G., Brown P.J., Maestre L., Hue S., Martinez-Torrecuadrada J.L., Ling K.L., Pratap S., Toms C., Fox B.C., Cerundolo V., Powrie F., Banham A.H. Analysis of FOXP3 protein expression in human CD4+CD25+ regulatory T cells at the single-cell level. Eur. J. Immunol. 2005, 35:1681-1691.
31. Rottman J.B., Willis C.R. Mouse models of systemic lupus erythematosus reveal a complex pathogenesis. Vet. Pathol. 2010, 47:664-676.
32. Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat. Immunol. 2005, 6:345-352.
33. Scheinecker C., Bonelli M., Smolen J.S. Pathogenetic aspects of systemic lupus erythematosus with an emphasis on regulatory T cells. J. Autoimmun. 2010, 35:269-275.
34. Tomura M., Honda T., Tanizaki H., Otsuka A., Egawa G., Tokura Y., Waldmann H., Hori S., Cyster J.G., Watanabe T., Miyachi Y., Kanagawa O., Kabashima K. Activated regulatory T cells are the major T cell type emigrating from the skin during a cutaneous immune response in mice. J. Clin. Invest. 2010, 120:883-893.
35. Valencia X., Stephens G., Goldbach-Mansky R., Wilson M., Shevach E.M., Lipsky P.E. TNF downmodulates the function of human CD4+CD25hi T-regulatory cells. Blood 2006, 108:253-261.
36. Valencia X., Yarboro C., Illei G., Lipsky P.E. Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus. J. Immunol. 2007, 178:2579-2588.
37. Vizi E.S., Orso E., Osipenko O.N., Hasko G., Elenkov I.J. Neurochemical, electrophysiological and immunocytochemical evidence for a noradrenergic link between the sympathetic nervous system and thymocytes. Neuroscience 1995, 68:1263-1276.
38. Wirth T., del Rey A. Apoptotic effect of noradrenaline on T regulatory cells. Exp. Dermatol. 2007, 16:382.
39. Wirth T., Wildmann J., Schäfer M.K., Besedovsky H.O., del Rey A. Regulatory T cells and the sympathetic nervous system in a murine model of autoimmune disease. Brain Behav. Immun. 2009, 23:S22.
40. Worth A., Thrasher A.J., Gaspar H.B. Autoimmune lymphoproliferative syndrome: molecular basis of disease and clinical phenotype. Br. J. Haematol. 2006, 133:124-140.
41. Zorn E., Nelson E.A., Mohseni M., Porcheray F., Kim H., Litsa D., Bellucci R., Raderschall E., Canning C., Soiffer R.J., Frank D.A., Ritz J. IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo. Blood 2006, 108:1571-1579.