{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:39:42Z","timestamp":1793227182931,"version":"4.5.0"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T00:00:00Z","timestamp":1584316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T00:00:00Z","timestamp":1584316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2013\/13691-1"],"award-info":[{"award-number":["2013\/13691-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2015\/23348-8"],"award-info":[{"award-number":["2015\/23348-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Daily oscillation of the immune system follows the central biological clock outputs control such as melatonin produced by the pineal gland. Despite the literature showing that melatonin is also synthesized by macrophages and T lymphocytes, no information is available regarding the temporal profile of the melatonergic system of immune cells and organs in steady-state. Here, the expression of the enzymes arylalkylamine-N-acetyltransferase (AA-NAT), its phosphorylated form (P-AA-NAT) and acetylserotonin-O-methyltransferase (ASMT) were evaluated in phagocytes and T cells of the bone marrow (BM) and spleen. We also determined how the melatonergic system of these cells is modulated by LPS and the cytokine IL-10. The expression of the melatonergic enzymes showed daily rhythms in BM and spleen cells. Melatonin rhythm in the BM, but not in the spleen, follows P-AA-NAT daily variation. In BM cells, LPS and IL10 induced an increase in melatonin levels associated with the increased expressions of P-AA-NAT and ASMT. In spleen cells, LPS induced an increase in the expression of P-AA-NAT but not of melatonin. Conversely, IL10 induced a significant increase in melatonin production associated with increased AA-NAT\/P-AA-NAT expressions. In conclusion, BM and spleen cells present different profiles of circadian production of local melatonin and responses to immune signals.<\/jats:p>","DOI":"10.1038\/s41598-020-61652-5","type":"journal-article","created":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T11:05:42Z","timestamp":1584356742000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Rhythmic expression of the melatonergic biosynthetic pathway and its differential modulation in vitro by LPS and IL10 in bone marrow and spleen"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8055-0085","authenticated-orcid":false,"given":"Marlina O.","family":"C\u00f3rdoba-Moreno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1419-5841","authenticated-orcid":false,"given":"Ewerton da Silva","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8493-6433","authenticated-orcid":false,"given":"Caroline L.","family":"Quiles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4613-187X","authenticated-orcid":false,"given":"D\u00e9bora","family":"dos Santos-Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1676-442X","authenticated-orcid":false,"given":"Gabriela S.","family":"Kinker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0118-5361","authenticated-orcid":false,"given":"Sandra M.","family":"Muxel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4606-6120","authenticated-orcid":false,"given":"Regina P.","family":"Markus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4871-8201","authenticated-orcid":false,"given":"Pedro A.","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,16]]},"reference":[{"key":"61652_CR1","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.jneuroim.2004.11.003","volume":"160","author":"L Marpeg\u00e1n","year":"2005","unstructured":"Marpeg\u00e1n, L., Bekinschtein, T. A., Costas, M. A. & Golombek, D. A. Circadian responses to endotoxin treatment in mice. J. Neuroimmunol. 160, 102\u2013109 (2005).","journal-title":"J. Neuroimmunol."},{"key":"61652_CR2","first-page":"149","volume":"36","author":"D Druzd","year":"2014","unstructured":"Druzd, D., Juan, A. D. & Scheiermann, C. Circadian rhythms in leukocyte trafficking. Semin Immunopathol 36, 149\u2013162 (2014).","journal-title":"Semin Immunopathol"},{"key":"61652_CR3","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.immuni.2014.02.002","volume":"40","author":"AM Curtis","year":"2014","unstructured":"Curtis, A. M., Bellet, M. M., Sassone-Corsi, P. & O\u2019Neill, L. A. J. Circadian Clock Proteins and Immunity. Immunity 40, 178\u2013186 (2014).","journal-title":"Immunity"},{"key":"61652_CR4","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1177\/0748730415577723","volume":"30","author":"N Labrecque","year":"2015","unstructured":"Labrecque, N. & Cermakian, N. Circadian Clocks in the Immune System. J. Biol. Rhythms 30, 277\u2013290 (2015).","journal-title":"J. Biol. Rhythms"},{"key":"61652_CR5","doi-asserted-by":"publisher","first-page":"4143","DOI":"10.1182\/blood-2003-03-0779","volume":"102","author":"DB Boivin","year":"2003","unstructured":"Boivin, D. B. et al. Circadian clock genes oscillate in human peripheral blood mononuclear cells. Blood 102, 4143\u20134145 (2003).","journal-title":"Blood"},{"key":"61652_CR6","doi-asserted-by":"publisher","first-page":"870","DOI":"10.3109\/07420528.2013.782315","volume":"30","author":"N Cermakian","year":"2013","unstructured":"Cermakian, N. et al. Crosstalk between the circadian clock circuitry and the immune system. Chronobiol. Int. 30, 870\u2013888 (2013).","journal-title":"Chronobiol. Int."},{"key":"61652_CR7","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1248\/bpb.30.621","volume":"30","author":"M Hayashi","year":"2007","unstructured":"Hayashi, M., Shimba, S. & Tezuka, M. Characterization of the molecular clock in mouse peritoneal macrophages. Biol. Pharm. Bull. 30, 621\u20136 (2007).","journal-title":"Biol. Pharm. Bull."},{"key":"61652_CR8","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1073\/pnas.1106750109","volume":"109","author":"JE Gibbs","year":"2011","unstructured":"Gibbs, J. E. et al. The nuclear receptor REV-ERB mediates circadian regulation of innate immunity through selective regulation of inflammatory cytokines. Proc. Natl. Acad. Sci. 109, 582\u2013587 (2011).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"61652_CR9","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.bbi.2014.11.009","volume":"45","author":"LK Fonken","year":"2015","unstructured":"Fonken, L. K. et al. Microglia inflammatory responses are controlled by an intrinsic circadian clock. Brain. Behav. Immun. 45, 171\u2013179 (2015).","journal-title":"Brain. Behav. Immun."},{"key":"61652_CR10","doi-asserted-by":"publisher","first-page":"21407","DOI":"10.1073\/pnas.0906361106","volume":"106","author":"M Keller","year":"2009","unstructured":"Keller, M. et al. A circadian clock in macrophages controls inflammatory immune responses. Proc. Natl. Acad. Sci. 106, 21407\u201321412 (2009).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"61652_CR11","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.immuni.2016.12.011","volume":"46","author":"D Druzd","year":"2017","unstructured":"Druzd, D. et al. Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses. Immunity 46, 120\u2013132 (2017).","journal-title":"Immunity"},{"key":"61652_CR12","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.bbi.2011.10.001","volume":"26","author":"AC Silver","year":"2012","unstructured":"Silver, A. C., Arjona, A., Hughes, M. E., Nitabach, M. N. & Fikrig, E. Circadian expression of clock genes in mouse macrophages, dendritic cells, and B cells. Brain Behav Immun. 26, 407\u2013413 (2012).","journal-title":"Brain Behav Immun."},{"key":"61652_CR13","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1124\/pr.55.2.2","volume":"55","author":"V Simonneaux","year":"2003","unstructured":"Simonneaux, V. & Ribelayga, C. Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters. Pharmacol. Rev. 55, 325\u2013395 (2003).","journal-title":"Pharmacol. Rev."},{"key":"61652_CR14","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1152\/physiol.00037.2015","volume":"31","author":"FN Buijs","year":"2016","unstructured":"Buijs, F. N. et al. The Circadian System: A Regulatory Feedback Network of Periphery and Brain. Physiology 31, 170\u2013181 (2016).","journal-title":"Physiology"},{"key":"61652_CR15","doi-asserted-by":"publisher","first-page":"8638","DOI":"10.3390\/ijms14048638","volume":"14","author":"A Carrillo-Vico","year":"2013","unstructured":"Carrillo-Vico, A., Lardone, P. J., Alvarez-Sanchez, N., Rodriguez-Rodriguez, A. & Guerrero, J. M. Melatonin: Buffering the immune system. Int. J. Mol. Sci. 14, 8638\u20138683 (2013).","journal-title":"Int. J. Mol. Sci."},{"key":"61652_CR16","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.1023\/A:1020107915919","volume":"47","author":"GA Bubenik","year":"2002","unstructured":"Bubenik, G. A. Gastrointestinal melatonin: Localization, function, and clinical relevance. Dig. Dis. Sci. 47, 2336\u20132348 (2002).","journal-title":"Dig. Dis. Sci."},{"key":"61652_CR17","doi-asserted-by":"publisher","first-page":"e52010","DOI":"10.1371\/journal.pone.0052010","volume":"7","author":"SM Muxel","year":"2012","unstructured":"Muxel, S. M. et al. NF-\u03baB drives the synthesis of melatonin in RAW 264.7 macrophages by inducing the transcription of the arylalkylamine-N-acetyltransferase (AA-NAT) gene. PLoS One 7, e52010 (2012).","journal-title":"PLoS One"},{"key":"61652_CR18","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1096\/fj.03-0694fje","volume":"18","author":"A Carrillo-Vico","year":"2004","unstructured":"Carrillo-Vico, A. et al. Evidence of melatonin synthesis by human lymphocytes and its physiological significance: possible role as intracrine, autocrine, and\/or paracrine substance. FASEB J. 18, 537\u2013539 (2004).","journal-title":"FASEB J."},{"key":"61652_CR19","doi-asserted-by":"publisher","first-page":"2182","DOI":"10.3390\/ijms19082182","volume":"19","author":"MA Pires-Lapa","year":"2018","unstructured":"Pires-Lapa, M. A., Carvalho-Sousa, C. E., Cecon, E., Fernandes, P. A. & Markus, R. P. \u03b2-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes. Int. J. Mol. Sci. 19, 2182 (2018).","journal-title":"Int. J. Mol. Sci."},{"key":"61652_CR20","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1089\/jir.1988.8.705","volume":"8","author":"LM Finocchiaro","year":"1988","unstructured":"Finocchiaro, L. M. et al. Serotonin and melatonin synthesis in peripheral blood mononuclear cells: stimulation by interferon-gamma as part of an immunomodulatory pathway. J.Interferon Res. 8, 705\u2013716 (1988).","journal-title":"J.Interferon Res."},{"key":"61652_CR21","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1111\/jpi.12321","volume":"60","author":"SM Muxel","year":"2016","unstructured":"Muxel, S. M., Laranjeira-Silva, M. F., Carvalho-Sousa, C. E., Floeter-Winter, L. M. & Markus, R. P. The RelA\/cRel nuclear factor- \u03ba B (NF-\u03ba B) dimer, crucial for inflammation resolution, mediates the transcription of the key enzyme in melatonin synthesis in RAW 264.7 macrophages. J. Pineal Res. 60, 394\u2013404 (2016).","journal-title":"J. Pineal Res."},{"key":"61652_CR22","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/S0304-4165(99)00125-7","volume":"1472","author":"DX Tan","year":"1999","unstructured":"Tan, D. X. et al. Identification of highly elevated levels of melatonin in bone marrow: Its origin and significance. Biochim. Biophys. Acta - Gen. Subj. 1472, 206\u2013214 (1999).","journal-title":"Biochim. Biophys. Acta - Gen. Subj."},{"key":"61652_CR23","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1034\/j.1600-079X.2000.280401.x","volume":"28","author":"A Conti","year":"2000","unstructured":"Conti, A. et al. Evidence for melatonin synthesis in mouse and human bone marrow cells. J. Pineal Res. 28, 193\u2013202 (2000).","journal-title":"J. Pineal Res."},{"key":"61652_CR24","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.exger.2009.02.002","volume":"44","author":"M Sanchez-Hidalgo","year":"2009","unstructured":"Sanchez-Hidalgo, M. et al. Age-related changes in melatonin synthesis in rat extrapineal tissues. Exp. Gerontol. 44, 328\u2013334 (2009).","journal-title":"Exp. Gerontol."},{"key":"61652_CR25","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/j.stem.2018.08.002","volume":"23","author":"K Golan","year":"2018","unstructured":"Golan, K. et al. Daily Onset of Light and Darkness Differentially Controls Hematopoietic Stem Cell Differentiation and Maintenance. Cell Stem Cell 23, 572\u2013585.e7 (2018).","journal-title":"Cell Stem Cell"},{"key":"61652_CR26","doi-asserted-by":"publisher","first-page":"3239","DOI":"10.1111\/bph.14083","volume":"175","author":"RP Markus","year":"2018","unstructured":"Markus, R. P., Fernandes, P. A., Kinker, G. S., da Silveira Cruz-Machado, S. & Marcola, M. Immune-pineal axis \u2013 acute inflammatory responses coordinate melatonin synthesis by pinealocytes and phagocytes. Br. J. Pharmacol. 175, 3239\u20133250 (2018).","journal-title":"Br. J. Pharmacol."},{"key":"61652_CR27","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1111\/j.1600-079X.2006.00373.x","volume":"41","author":"PACM Fernandes","year":"2006","unstructured":"Fernandes, P. A. C. M., Cecon, E., Markus, R. P. & Ferreira, Z. S. Effect of TNF-alpha on the melatonin synthetic pathway in the rat pineal gland: basis for a \u2018feedback\u2019 of the immune response on circadian timing. J. Pineal Res. 41, 344\u2013350 (2006).","journal-title":"J. Pineal Res."},{"key":"61652_CR28","first-page":"183","volume":"49","author":"S Da Silveira Cruz-Machado","year":"2010","unstructured":"Da Silveira Cruz-Machado, S. et al. TLR4 and CD14 receptors expressed in rat pineal gland trigger NFKB pathway. J. Pineal Res. 49, 183\u2013192 (2010).","journal-title":"J. Pineal Res."},{"key":"61652_CR29","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1371\/journal.pone.0013958","volume":"5","author":"EK Tamura","year":"2010","unstructured":"Tamura, E. K. et al. Long-lasting priming of endothelial cells by plasma melatonin levels. PLoS One 5, 7 (2010).","journal-title":"PLoS One"},{"issue":"9","key":"61652_CR30","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1002\/jcp.25300","volume":"231","author":"Marina Mar\u00e7ola","year":"2016","unstructured":"Marcola, M. et al. Light\/Dark Environmental Cycle Imposes a Daily Profile in the Expression of microRNAs in Rat CD133+ Cells. J. Cell. Physiol. 1\u201311, https:\/\/doi.org\/10.1002\/jcp.25300 (2016).","journal-title":"Journal of Cellular Physiology"},{"key":"61652_CR31","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1007\/s00429-013-0686-4","volume":"220","author":"L Pinato","year":"2013","unstructured":"Pinato, L. et al. Selective protection of the cerebellum against intracerebroventricular LPS is mediated by local melatonin synthesis. Brain Struct. Funct. 220, 827\u2013840 (2013).","journal-title":"Brain Struct. Funct."},{"key":"61652_CR32","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/S0014-2999(01)01369-3","volume":"430","author":"CMC Lotufo","year":"2001","unstructured":"Lotufo, C. M. C., Lopes, C., Dubocovich, M. L., Farsky, S. H. P. & Markus, R. P. Melatonin and N-acetylserotonin inhibit leukocyte rolling and adhesion to rat microcirculation. Eur. J. Pharmacol. 430, 351\u2013357 (2001).","journal-title":"Eur. J. Pharmacol."},{"key":"61652_CR33","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1111\/j.1600-079X.2006.00345.x","volume":"41","author":"GN Pontes","year":"2006","unstructured":"Pontes, G. N., Cardoso, E. C., Carneiro-Sampaio, M. M. S. & Markus, R. P. Injury switches melatonin production source from endocrine (pineal) to paracrine (phagocytes) - Melatonin in human colostrum and colostrum phagocytes. J. Pineal Res. 41, 136\u2013141 (2006).","journal-title":"J. Pineal Res."},{"key":"61652_CR34","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1111\/jpi.12066","volume":"55","author":"MA Pires-Lapa","year":"2013","unstructured":"Pires-Lapa, M. A., Tamura, E. K., Salustiano, E. M. A. & Markus, R. P. Melatonin synthesis in human colostrum mononuclear cells enhances dectin-1-mediated phagocytosis by mononuclear cells. J. Pineal Res. 55, 240\u2013246 (2013).","journal-title":"J. Pineal Res."},{"key":"61652_CR35","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1111\/j.1600-079X.2004.00191.x","volume":"38","author":"ZS Ferreira","year":"2005","unstructured":"Ferreira, Z. S. et al. Corticosterone modulates noradrenaline-induced melatonin synthesis through inhibition of nuclear factor kappa B. J. Pineal Res. 38, 182\u2013188 (2005).","journal-title":"J. Pineal Res."},{"key":"61652_CR36","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1111\/j.1365-2826.2008.01817.x","volume":"21","author":"PACM Fernandes","year":"2009","unstructured":"Fernandes, P. A. C. M. et al. Local corticosterone infusion enhances nocturnal pineal melatonin production in vivo. J. Neuroendocrinol. 21, 90\u201397 (2009).","journal-title":"J. Neuroendocrinol."},{"key":"61652_CR37","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1159\/000445189","volume":"104","author":"PA Fernandes","year":"2016","unstructured":"Fernandes, P. A. et al. Dual Effect of Catecholamines and Corticosterone Crosstalk on Pineal Gland Melatonin Synthesis. Neuroendocrinology 104, 126\u2013134 (2016).","journal-title":"Neuroendocrinology"},{"key":"61652_CR38","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1111\/jpi.12309","volume":"60","author":"LH Souza-Teodoro","year":"2016","unstructured":"Souza-Teodoro, L. H. et al. Adenosine triphosphate inhibits melatonin synthesis in the rat pineal gland. J. Pineal Res. 60, 242\u2013249 (2016).","journal-title":"J. Pineal Res."},{"key":"61652_CR39","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/j.1600-079X.2005.00220.x","volume":"39","author":"S Jimenez-Jorge","year":"2005","unstructured":"Jimenez-Jorge, S. et al. Melatonin synthesis and melatonin-membrane receptor (MT1) expression during rat thymus development: Role of the pineal gland. J. Pineal Res. 39, 77\u201383 (2005).","journal-title":"J. Pineal Res."},{"key":"61652_CR40","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1111\/j.1600-079X.2011.00931.x","volume":"52","author":"C Venegas","year":"2012","unstructured":"Venegas, C. et al. Extrapineal melatonin: Analysis of its subcellular distribution and daily fluctuations. J. Pineal Res. 52, 217\u2013227 (2012).","journal-title":"J. Pineal Res."},{"key":"61652_CR41","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.immuni.2012.05.021","volume":"37","author":"C Scheiermann","year":"2012","unstructured":"Scheiermann, C. et al. Adrenergic nerves govern circadian leukocyte recruitment to tissues. Immunity 37, 290\u2013301 (2012).","journal-title":"Immunity"},{"key":"61652_CR42","doi-asserted-by":"publisher","first-page":"2567","DOI":"10.1084\/jem.20160723","volume":"213","author":"K Suzuki","year":"2016","unstructured":"Suzuki, K., Hayano, Y., Nakaki, A., Furuta, F. & Noda, M. Adrenergic control of the adaptive immune response by diurnal lymphocyte recirculation through lymph nodes. J. Exp. Med. 213, 2567\u20132574 (2016).","journal-title":"J. Exp. Med."},{"key":"61652_CR43","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.immuni.2012.05.021","volume":"37","author":"C Scheiermann","year":"2013","unstructured":"Scheiermann, C. et al. Adrenergic Nerves Govern Circadian Leukocyte. Immunity 37, 290\u2013301 (2013).","journal-title":"Immunity"},{"key":"61652_CR44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/jpi.12189","volume":"58","author":"J Vriend","year":"2015","unstructured":"Vriend, J. & Reiter, R. J. Melatonin feedback on clock genes: A theory involving the proteasome. J. Pineal Res. 58, 1\u201311 (2015).","journal-title":"J. Pineal Res."},{"key":"61652_CR45","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1046\/j.1365-2826.2003.01001.x","volume":"15","author":"JH Stehle","year":"2003","unstructured":"Stehle, J. H., von Gall, C. & Korf, H. W. Melatonin: A clock-output, a clock-input. J. Neuroendocrinol. 15, 383\u2013389 (2003).","journal-title":"J. Neuroendocrinol."},{"key":"61652_CR46","doi-asserted-by":"crossref","unstructured":"Scanzano, A. & Cosentino, M. Adrenergic regulation of innate immunity: A review. Front. Pharmacol. 6 (2015).","DOI":"10.3389\/fphar.2015.00171"},{"key":"61652_CR47","doi-asserted-by":"publisher","unstructured":"Barbosa-Lima, L. E. et al. STAT1-NF\u03baB crosstalk triggered by interferon-gamma regulates noradrenaline-induced pineal hormonal production. Journal of Pineal Research, https:\/\/doi.org\/10.1111\/jpi.12599 (2019).","DOI":"10.1111\/jpi.12599"},{"key":"61652_CR48","doi-asserted-by":"crossref","first-page":"5163","DOI":"10.4049\/jimmunol.158.11.5163","volume":"158","author":"N Petrovsky","year":"1997","unstructured":"Petrovsky, N. & Harrison, L. C. Diurnal Rhythmicity of Human Cytokine Production A Dynamic Disequilibrium in T Helper Cell Type 1\/T Helper Cell Type 2 Balance? J. Immunol. 158, 5163\u20135168 (1997).","journal-title":"J. Immunol."},{"key":"61652_CR49","doi-asserted-by":"publisher","first-page":"167","DOI":"10.2174\/1568026023394335","volume":"2","author":"JM Guerrero","year":"2002","unstructured":"Guerrero, J. M. & Reiter, R. J. Melatonin-immune system relationships. Curr. Top. Med. Chem. 2, 167\u201379 (2002).","journal-title":"Curr. Top. Med. Chem."},{"key":"61652_CR50","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1385\/ENDO:27:2:087","volume":"27","author":"RJ Reiter","year":"2005","unstructured":"Reiter, R. J., Carrillo-Vico, A., Guerrero, J. M. & Lardone, P. J. A Review of the Multiple Actions of Melatonin on the Immune System. Endocrine 27, 189\u2013200 (2005).","journal-title":"Endocrine"},{"key":"61652_CR51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/jpi.12394","volume":"62","author":"W Ren","year":"2017","unstructured":"Ren, W. et al. Melatonin signaling in T cells: Functions and applications. J. Pineal Res. 62, 1\u201315 (2017).","journal-title":"J. Pineal Res."},{"key":"61652_CR52","first-page":"215","volume":"24","author":"GH El-sokkary","year":"2003","unstructured":"El-sokkary, G. H., Reiter, R. J. & Abdel-ghaffar, S. K. Melatonin supplementation restores cellular proliferation and DNA synthesis in the splenic and thymic lymphocytes of old rats. Neuroendocrinol. Lett. 24, 215\u2013223 (2003).","journal-title":"Neuroendocrinol. Lett."},{"key":"61652_CR53","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/S0047-6374(98)00046-3","volume":"103","author":"D Atre","year":"1998","unstructured":"Atre, D. & Blumenthal, E. J. Melatonin: immune modulation of spleen cells in young, middle-aged and senescent mice. Mech. Ageing Dev. 103, 255\u2013268 (1998).","journal-title":"Mech. Ageing Dev."},{"key":"61652_CR54","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1111\/jpi.12279","volume":"59","author":"MF Laranjeira-Silva","year":"2015","unstructured":"Laranjeira-Silva, M. F., Zampieri, R. A., Muxel, S. M., Floeter-Winter, L. M. & Markus, R. P. Melatonin attenuates Leishmania (L.) amazonensis infection by modulating arginine metabolism. J. Pineal Res. 59, 478\u2013487 (2015).","journal-title":"J. Pineal Res."},{"key":"61652_CR55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fcimb.2019.00060","volume":"9","author":"JCR Fernandes","year":"2019","unstructured":"Fernandes, J. C. R. et al. Melatonin and Leishmania amazonensis Infection Altered miR-294, miR-30e, and miR-302d Impacting on Tnf, Mcp-1, and Nos2 Expression. Front. Cell. Infect. Microbiol. 9, 1\u201315 (2019).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"61652_CR56","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1111\/j.1476-5381.1994.tb13037.x","volume":"112","author":"ZS Ferreira","year":"1994","unstructured":"Ferreira, Z. S., Cipolla-Neto, J. & Markus, R. P. Presence of P2\u2010purinoceptors in the rat pineal gland. Br. J. Pharmacol. 112, 107\u2013110 (1994).","journal-title":"Br. J. Pharmacol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-61652-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-61652-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-61652-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T17:52:35Z","timestamp":1695923555000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-61652-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,16]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["61652"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-61652-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,16]]},"assertion":[{"value":"26 September 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4799"}}