Melatonin signaling in T cells: Functions and applications

Journal of Pineal Research

Volumn 62, Issue 3, 2017, Pages

  Ren, Wenkai ^a,b,c   Liu, Gang ^a   Chen, Shuai ^a   Yin, Jie ^a   Wang, Jing ^a   Tan, Bie ^a   Wu, Guoyao ^d   Bazer, Fuller W ^d   Peng, Yuanyi ^e   Li, Tiejun ^a,f   Reiter, Russel J ^g   Yin, Yulong ^a,b,h  

^a INSTITUTE OF GEOLOGY AND GEOPHYSICS   (China)

^b SOUTH CHINA AGRICULTURAL UNIVERSITY   (China)

^c UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

^d TEXAS A AND M UNIVERSITY   (United States)

^e SOUTHWEST UNIVERSITY   (China)

^f HUNAN CO INNOVATION CENTER OF ANIMAL PRODUCTION SAFETY   (China)

^g University of Texas Health Science Center   (United States)

^h HUNAN NORMAL UNIVERSITY   (China)

Author keywords

melatonin; multiple sclerosis; systemic lupus erythematosus; T cells; Th17 cells; Treg cells

Indexed keywords

CCAAT ENHANCER BINDING PROTEIN ALPHA; CELL NUCLEUS RECEPTOR; MELATONIN; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; CCAAT ENHANCER BINDING PROTEIN; CEBPA PROTEIN, HUMAN; MAPK1 PROTEIN, HUMAN;

CELL ACTIVATION; CELL SURVIVAL; CYTOLOGY; HORMONE SYNTHESIS; HUMAN; INSULIN DEPENDENT DIABETES MELLITUS; INTRACELLULAR SIGNALING; LYMPHOCYTE DIFFERENTIATION; MEMORY T LYMPHOCYTE; MULTIPLE SCLEROSIS; NONHUMAN; REGULATORY T LYMPHOCYTE; REVIEW; SYSTEMIC LUPUS ERYTHEMATOSUS; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TH17 CELL; ANIMAL; IMMUNOLOGY; PATHOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; CCAAT-ENHANCER-BINDING PROTEINS; DIABETES MELLITUS, TYPE 1; HUMANS; LUPUS ERYTHEMATOSUS, SYSTEMIC; MAP KINASE SIGNALING SYSTEM; MITOGEN-ACTIVATED PROTEIN KINASE 1; MITOGEN-ACTIVATED PROTEIN KINASE 3; MULTIPLE SCLEROSIS; T-LYMPHOCYTES, REGULATORY; TH17 CELLS;

EID: 85014027195     PISSN: 07423098     EISSN: 1600079X     Source Type: Journal    
DOI: 10.1111/jpi.12394     Document Type: Review

References (189)

1. Stehle JH, Saade A, Ackermann K, et al. A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases. J Pineal Res. 2011;51:17–43.
2. Tan DX, Hardeland R, Back K, et al. On the significance of an alternate pathway of melatonin synthesis via 5-methoxytryptamine: comparisons across species. J Pineal Res. 2016;61:27–40.
3. Back K, Tan DX, Reiter RJ. Melatonin biosynthesis in plants: multiple pathways catalyze tryptophan to melatonin in the cytoplasm or chloroplasts. J Pineal Res. 2016;61:426–437.
4. Byeon Y, Tan DX, Reiter RJ, et al. Predominance of 2-hydroxymelatonin over melatonin in plants. J Pineal Res. 2015;59:448–454.
5. Lerner AB, Case JD, Takahashi Y, et al. Isolation of melatonin, the pineal gland factor that lightens melanocytes. J Am Chem Soc. 1958;80:2587.
6. Quay WB. Circadian and estrous rhythms in pineal melatonin and 5-hydroxy indole-3-acetic acid. Proc Soc Exp Biol Med. 1964;115:710–713.
7. Wurtman RJ, Axelrod J, Fischer JE. Melatonin synthesis in the pineal gland: effect of light mediated by the sympathetic nervous system. Science. 1964;143:1328–1329.
8. Reiter RJ, King TS, Richardson BA, et al. Studies on pineal melatonin levels in a diurnal species, the eastern chipmunk (Tamias striatus): effect of light at night, propranolol administration or superior cervical ganglionectomy. J Neurol Transm. 1982;54:275–284.
9. Griffiths DJ, Bryden MM, Kennaway DJ. A fluctuation in plasma melatonin level in the Weddell seal during constant natural light. J Pineal Res. 1986;3:127–134.
10. Blank JL, Nelson RJ, Vaughan MK, et al. Pineal melatonin content in photoperiodically responsive and non-responsive phenotypes of deer mice. Comp Biochem Physiol A Comp Physiol. 1988;91:535–537.
11. Eloranta E, Timisjarvi J, Neiminen M, et al. Seasonal and daily rhythms in melatonin secretion in female reindeer and their calves. Endocrinology. 1999;130:1645–1652.
12. Reiter RJ, Steinlechner S, Richardson BA, et al. Differential response of pineal melatonin levels to light at night in laboratory-raised and wild-captured 13-lined ground squirrels (Spermophilus tridecemlineatus). Life Sci. 1983;32:2625–2629.
13. Reiter RJ, Reiter MN, Hattori A, et al. The pineal melatonin rhythm and its regulation by light in a subterranean rodent, the valley pocket gopher (Thomomys bottae). J Pineal Res. 1994;16:145–153.
14. Borjigin J, Li X, Snyder SH. The pineal gland and melatonin: molecular and pharmacological regulation. Ann Rev Pharmacol Toxicol. 1999;39:53–65.
15. Haldar C, Barbar R. Reproductive phase dependent circadian variation in the pineal biochemical constituents of Indian palm squirrel, Funambulus pennanti. Acta Biol Hung. 2001;52:9–15.
16. Aarseth JJ, Van't Hof TJ, Stokkan KA. Melatonin is a rhythmic in newborn seals exposed to continuous light. J Comp Physiol. 2003;173:37–42.
17. El Allali K, Sinikskaya N, Bothorel B, et al. Daily Aa-nat gene expression in the camel (Camelus dromedarius) pineal gland. Chronobiol Int. 2008;25:800–807.
18. Quay WB. Retinal and pineal hydroxyindole-O-methyltransferase activity in vertebrates. Life Sci. 1965;4:983–991.
19. Nagle CA, Cardinali DP, Rosner JM. Light regulation of rat retinal hydroxyindole-O-methyl transferase (HIOMT) activity. Endocrinology. 1972;91:423–426.
20. Pang SF, Brown GM, Groto LJ, et al. Determination of N-acetylserotonin and melatonin activities in the pineal gland, retina, Harderian gland, brain and serum of rats and chickens. Neuroendocrinology. 1977;23:1–13.
21. Vivien-Roels B, Pevet P, Dubois MP, et al. Immunohistochemical evidence for the presence of melatonin in the pineal gland, the retina and the Harderian gland. Cell Tissue Res. 1981;217:105–115.
22. Mennenga K, Ueck M, Reiter RJ. Immunohistological localization of melatonin in the pineal gland and retina of the rat. J Pineal Res. 1991;10:159–164.
23. Brammer GL, Yuwiler A, Wetterberg L. N-acetyltransferase activity of the rat harderian gland. Biochim Biophys Acta. 1978;526:93–99.
24. Mhatre MC, van Jaarsveld AS, Reiter RJ. Melatonin in the lacrimal gland: first demonstration and experimental manipulation. Biochem Biophys Res Commun. 1988;153:1186–1192.
25. Abe M, Itoh MT, Miyata M, et al. Detection of melatonin, its precursors and related enzyme activities in rabbit lens. Exp Eye Res. 1999;68:255–262.
26. Alkozi HA, Wang X, Perez de Lara MJ, et al. Presence of melanopsin in human crystalline lens epithelial cells and its role in melatonin synthesis. Exp Eye Res. 2016;154:168–176.
27. Raikhlin NT, Kvetnoy IM, Tolkachev VN. Melatonin may be synthesised in enterochromaffin cells. Nature. 1975;255:344–345.
28. Bubenik GA, Brown GM, Groto LJ. Immunocytochemical localization of melatonin in the rat gastrointestinal system. Experientia. 1977;53:373–382.
29. Brammer GL. Duodenum is not a consistent source of melatonin in rats. Life Sci. 1994;55:775–787.
30. Sanchez-Hidalgo M, de la Lastra CA, Carrascosa-Salmoral MP, et al. Age-related changes in melatonin synthesis in rat extrapineal tissues. Exp Gerontol. 2009;44:328–334.
31. Venegas C, Garcia JA, Escames G, et al. Extrapineal melatonin: analysis of its subcellular distribution and daily fluctuations. J Pineal Res. 2012;52:217–227.
32. Soderquist F, Hellstrom PM, Cunningham JL. Human gastroenteropancreatic expression of melatonin and its receptors MT1 and MT2. PLoS One. 2015;10:e0120195.
33. Menendez A, Poeggler B, Reiter RJ, et al. Nuclear localization of melatonin in different mammalian tissues: immunocytochemical and radioimmunoassay evidence. J Cell Biochem. 1993;53:373–382.
34. Jimenez-Jorge S, Jimenez-Caliani AJ, Guerrero JM, et al. Melatonin synthesis and melatonin-membrane receptor (MT1) expression during rat thymus development: role of the pineal gland. J Pineal Res. 2005;39:77–83.
35. Garcia-Marin R, de Miguel M, Fernandez-Santos JM, et al. Melatonin-synthesizing enzymes and melatonin receptor in rat thyroid cells. Histol Histopathol. 2012;27:1429–1438.
36. Tan DX, Manchester LC, Reiter RJ, et al. Identification of highly elevated levels of melatonin in bone marrow: its origin and significance. Biochim Biophys Acta. 1999;1472:206–214.
37. Conti A, Conconi S, Hertens E, et al. Evidence for melatonin synthesis by bone marrow cells. J Pineal Res. 2000;28:193–202.
38. Carrillo-Vico A, Calvo JR, Abreu P, et al. Evidence of mle synthesis by human lymphocytes and its physiological significance: possible role as intracine, autocrine and/or paracrine substance. FASEB J. 2004;18:537–539.
39. Biesalski HK, Welker HA, Thalmann R, et al. Melatonin and other serotonin derivatives in the guinea pig membranous cochlea. Neurosci Lett. 1988;91:41–46.
40. Lopez-Gonzalez MA, Guerrero JM, Delgado F. Presence of the pineal hormone melatonin in the rat cochlea: its variations with lighting conditions. Neurosci Lett. 1997;238:81–83.
41. Gonzalez-Arto M, Hamilton TR, Gallego M, et al. Evidence of melatonin synthesis in the ram reproductive tract. Andrology. 2016;4:163–171.
42. Sakaguchi K, Itoh MT, Takahashi N, et al. The rat oocyte synthesises melatonin. Reprod Fertil Dev. 2013;25:674–682.
43. He C, Wang J, Zhang Z, et al. Mitochondria synthesize melatonin to ameliorate its function and improve mice oocyte's quality under in vitro conditions. Int J Mol Sci. 2016;17:E939. in press.
44. Slominski A, Baker J, Rosano TG, et al. Metabolism of serotonin to N-acetylserotonin, melatonin, and 5-methoxytryptamine in hamster skin culture. J Biol Chem. 1996;271:12281–12286.
45. Slominski A, Tobin DJ, Zmijewski MA, et al. Melatonin in the skin: synthesis, metabolism and functions. Trends Endocrinol Metab. 2008;19:17–24.
46. Slominski A, Kleszczynski K, Semak I, et al. Local melatonergic system as a protector of skin integrity. Int J Mol Sci. 2014;15:17705–17732.
47. Acuna-Castroviejo D, Escames G, Venegas C, et al. Extrapineal melatonin: sources, regulation, and potential functions. Cell Mol Life Sci. 2014;71:2997–3025.
48. Dubbels R, Reiter RJ, Klenke E, et al. Melatonin in edible plants identified by radioimmunoassay and by high performance liquid chromatography-mass spectrometry. J Pineal Res. 1995;18:28–31.
49. Hattori A, Migitaka H, Iigo M, et al. Identification of melatonin in plants and its effects on plasma melatonin levels and binding to melatonin receptors in vertebrates. Biochem Mol Biol Int. 1995;35:627–634.
50. Manchester LC, Poeggeler B, Alvares FL, et al. Melatonin immunoreactivity in the photosynthetic prokaryote Rhodospirillum rubrum: implications for an ancient antioxidant system. Cell Mol Biol Res. 1995;41:391–395.
51. Migliori ML, Romanowski A, Simonetta SH, et al. Daily variation in melatonin synthesis and arylalkylamine N-acetyltransferase activity in the nematode Caenorhabditis elegans. J Pineal Res. 2012;53:38–46.
52. Tosches MA, Bucher D, Vopalensky P, et al. Melatonin signaling controls circadian swimming behavior in marine zooplankton. Cell. 2014;159:46–47.
53. Lee K, Zawadzka A, Czarvocki Z, et al. Molecular cloning of melatonin 3-hydroxylase and its production of cyclic-3-hydroxymelatonin in rice (Oryza sativa). J Pineal Res. 2016;61:470–478.
54. Byeon Y, Lee HJ, Lee HY, et al. Cloning and functional characterization of the arabidopsis N-acetylserotonin O-methyltransferase responsible for melatonin synthesis. J Pineal Res. 2016;60:65–73.
55. Dragojevic Dikic S, Jovanovic AM, Dikic S, et al. Melatonin: a “Higgs boson” in human reproduction. Gynecol Endocrinol. 2015;31:92–101.
56. Miller E, Morel A, Saso L, et al. Melatonin redox activity: its potential clinical application in neurodegenerative disorders. Curr Top Med Chem. 2015;15:163–169.
57. Vriend J, Reiter RJ. Melatonin feedback in clock genes: a theory involving the proteasome. J Pineal Res. 2015;58:1–11.
58. Manchester LC, Coto-Montes A, Boga JA, et al. Melatonin: an ancient molecule that makes oxygen metabolically tolerable. J Pineal Res. 2015;59:403–419.
59. Sanchez-Barcelo EJ, Mediavilla MD, Vriend J, et al. Constitutive photomorphogenesis protein 1 (COP1) and COP9 signalosome, evolutionarily conserved photomorphogenic proteins as possible targets of melatonin. J Pineal Res. 2016;61:41–51.
60. Hosseinzadeh A, Kamrava SK, Joghataei MT, et al. Apoptosis signaling pathways in osteoarthritis and possible protective role of melatonin. J Pineal Res. 2016;61:411–425.
61. Golombek DA, Pandi-Perumal SR, Brown GM, et al. Some implications of melatonin use in chronopharmacology of insomnia. Eur J Pharmacol. 2015;762:42–48.
62. Opie LH, Lecour S. Melatonin has multiorgan effects. Eur Heart J Cardiovasc Pharmacother. 2016;2:258–265.
63. Reiter RJ, Mayo JC, Tan DX, et al. Melatonin as an antioxidant: under promises but over delivers. J Pineal Res. 2016;61:253–278.
64. Reiter RJ, Tan DX, Manchester LC, et al. Medical implications of melatonin: receptor-mediated and receptor-independent actions. Adv Med Sci. 2007;52:11–28.
65. Tan DX, Hardeland R, Manchester LC, et al. The changing biological roles of melatonin during evolution: from an antioxidant to signals of darkness, sexual selection and fitness. Biol Rev Camb Philos Soc. 2010;85:607–623.
66. Slominski RM, Reiter RJ, Schlabritz-Loutsevitch N, et al. Melatonin membrane receptors in peripheral tissues: distribution and functions. Mol Cell Endocrinol. 2012;351:152–166.
67. Reiter RJ, Tan DX, Galano A. Melatonin: exceeding expectations. Physiology (Bethesda). 2014;29:325–333.
68. He B, Zhao Y, Xu L, et al. The nuclear melatonin receptor RORalpha is a novel endogenous defender against myocardial ischemia/reperfusion injury. J Pineal Res. 2016;60:313–326.
69. Jockers R, Delagrange P, Dubocovich ML, et al. Update on melatonin receptors: IUPHAR Review 20. Br J Pharmacol. 2016;173:2702–2725.
70. Pozo D, Reiter RJ, Calvo JR, et al. Inhibition of cerebellar nitric oxide synthase and cyclic GMP production of melatonin via complex formation with calmodulin. J Cell Biochem. 1997;65:430–442.
71. Macias M, Escames G, Leon J, et al. Calreticulin melatonin. An unexpected relationship. Eur J Biochem. 2003;270:832–840.
72. Boutin JA. Quinone reductase 2 as a promising target of melatonin therapeutic actions. Expert Opin Ther Targets. 2016;20:303–317.
73. Alvarez-Sanchez N, Cruz-Chamorro I, Lopez-Gonzalez A, et al. Melatonin controls experimental autoimmune encephalomyelitis by altering the T effector/regulatory balance. Brain Behav Immun. 2015;50:101–114.
74. Brazao V, Colato RP, Santello FH, et al. Interleukin-17, oxidative stress, and inflammation: role of melatonin during Trypanosoma cruzi infection. J Pineal Res. 2015;59:488–496.
75. Farez MF, Mascanfroni ID, Mendez-Huergo SP, et al. Melatonin contributes to the seasonality of multiple sclerosis relapses. Cell. 2015;162:1338–1352.
76. Lopez-Gonzalez A, Alvarez-Sanchez N, Lardone PJ, et al. Melatonin treatment improves primary progressive multiple sclerosis: a case report. J Pineal Res. 2015;58:173–177.
77. Muxel SM, Laranjeira-Silva MF, Cavalho-Sausa CE, et al. Melatonin alleviates acute lung injury through inhibiting the NLRP3 inflammasome. J Pineal Res. 2016;60:405–414.
78. Lacoste B, Angeloni D, Dominguez-Lopez S, et al. Anatomical and cellular localization of melatonin MT1 and MT2 receptors in the adult rat brain. J Pineal Res. 2015;58:397–417.
79. Reppert SM, Weaver DR, Godson C. Melatonin receptors step into the light: cloning and classification of subtypes. Trends Pharmacol Sci. 1996;17:100–102.
80. Reppert SM. Melatonin receptors: molecular biology of a new family of G protein-coupled receptors. J Biol Rhythms. 1997;12:528–531.
81. Sugden D, Davidson K, Hough KA, et al. Melatonin, melatonin receptors and melanophores: a moving story. Pigment Cell Res. 2004;17:454–460.
82. Becker-Andre M, Wiesenberg I, Schaeren-Wiemers N, et al. Pineal gland hormone melatonin binds and activates an orphan of the nuclear receptor superfamily. J Biol Chem. 1994;269:28531–28534.
83. Lardone PJ, Guerrero JM, Fernandez-Santos JM, et al. Melatonin synthesized by T lymphocytes as a ligand of the retinoic acid-related orphan receptor. J Pineal Res. 2011;51:454–462.
84. Becker-Andre M, Andre E, DeLamarter JF. Identification of nuclear receptor mRNAs by RT-PCR amplification of conserved zinc-finger motif sequences. Biochem Biophys Res Commun. 1993;194:1371–1379.
85. Carlberg C, Hooft van Huijsduijnen R, Staple JK, et al. RZRs, a new family of retinoid-related orphan receptors that function as both monomers and homodimers. Mol Endocrinol. 1994;8:757–770.
86. Hirose T, Smith RJ, Jetten AM. ROR gamma: the third member of ROR/RZR orphan receptor subfamily that is highly expressed in skeletal muscle. Biochem Biophys Res Commun. 1994;205:1976–1983.
87. Gonzalez-Haba MG, Garcia-Maurino S, Calvo JR, et al. High-affinity binding of melatonin by human circulating T lymphocytes (CD4+). FASEB J. 1995;9:1331–1335.
88. Pozo D, Delgado M, Fernandez-Santos JM, et al. Expression of the Mel1a-melatonin receptor mRNA in T and B subsets of lymphocytes from rat thymus and spleen. FASEB J. 1997;1997:466–473.
89. Guerrero JM, Pozo D, Garcia-Maurino S, et al. Involvement of nuclear receptors in the enhanced IL-2 production by melatonin in Jurkat cells. Ann N Y Acad Sci. 2000;917:397–403.
90. Lardone PJ, Carrillo-Vico A, Naranjo MC, et al. Melatonin synthesized by Jurkat human leukemic T cell line is implicated in IL-2 production. J Cell Physiol. 2006;206:273–279.
91. Pozo D, Garcia-Maurino S, Guerrero JM, et al. mRNA expression of nuclear receptor RZR/RORalpha, melatonin membrane receptor MT, and hydroxindole-O-methyltransferase in different populations of human immune cells. J Pineal Res. 2004;37:48–54.
92. Chen Y, Leon-Ponte M, Pingle SC, et al. T lymphocytes possess the machinery for 5-HT synthesis, storage, degradation and release. Acta Physiol (Oxf). 2015;213:860–867.
93. Ha E, Han E, Park HJ, et al. Microarray analysis of transcription factor gene expression in melatonin-treated human peripheral blood mononuclear cells. J Pineal Res. 2006;40:305–311.
94. Rothenberg EV, Moore JE, Yui MA. Launching the T-cell-lineage developmental programme. Nat Rev Immunol. 2008;8:9–21.
95. Rothenberg EV. Transcriptional control of early T and B cell developmental choices. Annu Rev Immunol. 2014;32:283–321.
96. MacIver NJ, Michalek RD, Rathmell JC. Metabolic regulation of T lymphocytes. Annu Rev Immunol. 2013;31:259–283.
97. Tian YM, Li PP, Jiang XF, et al. Rejuvenation of degenerative thymus by oral melatonin administration and the antagonistic action of melatonin against hydroxyl radical-induced apoptosis of cultured thymocytes in mice. J Pineal Res. 2001;31:214–221.
98. El-Sokkary GH, Reiter RJ, Abdel-Ghaffar S. Melatonin supplementation restores cellular proliferation and DNA synthesis in the splenic and thymic lymphocytes of old rats. Neuro Endocrinol Lett. 2003;24:215–223.
99. Sokolovic D, Djordjevic B, Kocic G, et al. Melatonin protects rat thymus against oxidative stress caused by exposure to microwaves and modulates proliferation/apoptosis of thymocytes. Gen Physiol Biophys. 2013;32:79–90.
100. Reiter RJ, Richardson BA, Johnson LY, et al. Pineal melatonin rhythm: reduction in aging Syrian hamsters. Science. 1980;210:1372–1373.
101. Reiter RJ, Craft CM, Johnson JE, et al. Age-associated reduction in nocturnal pineal melatonin levels in female rats. Endocrinology. 1981;109:1295–1297.
102. Sack RL, Lewy AJ, Erb DL, et al. Human melatonin production decreases with age. J Pineal Res. 1986;3:379–388.
103. Smith GA, Uchida K, Weiss A, et al. Essential biphasic role for JAK3 catalytic activity in IL-2 receptor signaling. Nat Chem Biol. 2016;12:373–379.
104. Bensinger SJ, Walsh PT, Zhang J, et al. Distinct IL-2 receptor signaling pattern in CD4+CD25+ regulatory T cells. J Immunol. 2004;172:5287–5296.
105. Kuhlwein E, Irwin M. Melatonin modulation of lymphocyte proliferation and Th1/Th2 cytokine expression. J Neuroimmunol. 2001;117:51–57.
106. Garcia-Maurino S, Gonzalez-Haba MG, Calvo JR, et al. Melatonin enhances IL-2, IL-6, and IFN-gamma production by human circulating CD4+ cells: a possible nuclear receptor-mediated mechanism involving T helper type 1 lymphocytes and monocytes. J Immunol. 1997;159:574–581.
107. Raghavendra V, Singh V, Shaji AV, et al. Melatonin provides signal 3 to unprimed CD4(+) T cells but failed to stimulate LPS primed B cells. Clin Exp Immunol. 2001;124:414–422.
108. Yoo YM, Jang SK, Kim GH, et al. Pharmacological advantages of melatonin in immunosenescence by improving activity of T lymphocytes. J Biomed Res. 2016;30:314–321.
109. Chen F, Reheman A, Cao J, et al. Effect of melatonin on monochromatic light-induced T-lymphocyte proliferation in the thymus of chickens. J Photochem Photobiol B. 2016;161:9–16.
110. Lardone PJ, Rubio A, Cerrillo I, et al. Blocking of melatonin synthesis and MT(1) receptor impairs the activation of Jurkat T cells. Cell Mol Life Sci. 2010;67:3163–3172.
111. Raphael I, Nalawade S, Eagar TN, et al. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine. 2015;74:5–17.
112. Chen K, Kolls JK. T cell-mediated host immune defenses in the lung. Annu Rev Immunol. 2013;31:605–633.
113. Vahedi G, C Poholek A, Hand TW, et al. Helper T-cell identity and evolution of differential transcriptomes and epigenomes. Immunol Rev. 2013;252:24–40.
114. Wu M, Xiao H, Liu G, et al. Glutamine promotes intestinal SIgA secretion through intestinal microbiota and IL-13. Mol Nutr Food Res. 2016;60:1637–1648.
115. Chapoval S, Dasgupta P, Dorsey NJ, et al. Regulation of the T helper cell type 2 (Th2)/T regulatory cell (Treg) balance by IL-4 and STAT6. J Leukoc Biol. 2010;87:1011–1018.
116. Zhao P, Xiao X, Ghobrial RM, et al. IL-9 and Th9 cells: progress and challenges. Int Immunol. 2013;25:547–551.
117. Schmitt E, Klein M, Bopp T. Th9 cells, new players in adaptive immunity. Trends Immunol. 2014;35:61–68.
118. Pan HF, Leng RX, Li XP, et al. Targeting T-helper 9 cells and interleukin-9 in autoimmune diseases. Cytokine Growth Factor Rev. 2013;24:515–522.
119. Kaplan MH, Hufford MM, Olson MR. The development and in vivo function of T helper 9 cells. Nat Rev Immunol. 2015;15:295–307.
120. Miossec P, Kolls JK. Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov. 2012;11:763–776.
121. Wilson NJ, Boniface K, Chan JR, et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol. 2007;8:950–957.
122. Ivanov II, Zhou L, Littman DR. Transcriptional regulation of Th17 cell differentiation. Semin Immunol. 2007;19:409–417.
123. Shabgah AG, Fattahi E, Shahneh FZ. Interleukin-17 in human inflammatory diseases. Postepy Dermatol Alergol. 2014;31:256–261.
124. McGeachy MJ, Cua DJ. Th17 cell differentiation: the long and winding road. Immunity. 2008;28:445–453.
125. Floss DM, Schroder J, Franke M, et al. Insights into IL-23 biology: from structure to function. Cytokine Growth Factor Rev. 2015;26:569–578.
126. Nagai S, Kurebayashi Y, Koyasu S. Role of PI3K/Akt and mTOR complexes in Th17 cell differentiation. Ann N Y Acad Sci. 2013;1280:30–34.
127. Kim JS, Sklarz T, Banks LB, et al. Natural and inducible TH17 cells are regulated differently by Akt and mTOR pathways. Nat Immunol. 2013;14:611–618.
128. Ren W, Yin J, Duan J, et al. mTORC1 signaling and IL-17 expression: defining pathways and possible therapeutic targets. Eur J Immunol. 2016;46:291–299.
129. Trifari S, Kaplan CD, Tran EH, et al. Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells. Nat Immunol. 2009;10:864–871.
130. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299:1057–1061.
131. Carrier Y, Yuan J, Kuchroo VK, et al. Th3 cells in peripheral tolerance. I. Induction of Foxp3-positive regulatory T cells by Th3 cells derived from TGF-beta T cell-transgenic mice. J Immunol. 2007;178:179–185.
132. Bommireddy R, Doetschman T. TGFbeta1 and Treg cells: alliance for tolerance. Trends Mol Med. 2007;13:492–501.
133. Schmitt N, Ueno H. Regulation of human helper T cell subset differentiation by cytokines. Curr Opin Immunol. 2015;34:130–136.
134. Miyara M, Sakaguchi S. Natural regulatory T cells: mechanisms of suppression. Trends Mol Med. 2007;13:108–116.
135. Ueno H, Banchereau J, Vinuesa CG. Pathophysiology of T follicular helper cells in humans and mice. Nat Immunol. 2015;16:142–152.
136. Crotty S. Follicular helper CD4 T cells (TFH). Annu Rev Immunol. 2011;29:621-663.
137. Nakayamada S, Kanno Y, Takahashi H, et al. Early Th1 cell differentiation is marked by a Tfh cell-like transition. Immunity. 2011;35:919–931.
138. Schmitt N, Liu Y, Bentebibel SE, et al. The cytokine TGF-beta co-opts signaling via STAT3-STAT4 to promote the differentiation of human TFH cells. Nat Immunol. 2014;15:856–865.
139. Schmitt N, Bustamante J, Bourdery L, et al. IL-12 receptor beta1 deficiency alters in vivo T follicular helper cell response in humans. Blood. 2013;121:3375–3385.
140. Schmitt N, Morita R, Bourdery L, et al. Human dendritic cells induce the differentiation of interleukin-21-producing T follicular helper-like cells through interleukin-12. Immunity. 2009;31:158–169.
141. Nurieva RI, Chung Y, Hwang D, et al. Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity. 2008;29:138–149.
142. Suto A, Kashiwakuma D, Kagami S, et al. Development and characterization of IL-21-producing CD4+ T cells. J Exp Med. 2008;205:1369–1379.
143. Medrano-Campillo P, Sarmiento-Soto H, Alvarez-Sanchez N, et al. Evaluation of the immunomodulatory effect of melatonin on the T-cell response in peripheral blood from systemic lupus erythematosus patients. J Pineal Res. 2015;58:219–226.
144. Shaji AV, Kulkarni SK, Agrewala JN. Regulation of secretion of IL-4 and IgG1 isotype by melatonin-stimulated ovalbumin-specific T cells. Clin Exp Immunol. 1998;111:181–185.
145. Liu H, Xu L, Wei JE, et al. Role of CD4+ CD25+ regulatory T cells in melatonin-mediated inhibition of murine gastric cancer cell growth in vivo and in vitro. Anat Rec (Hoboken). 2011;294:781-788.
146. Vigore L, Messina G, Brivio F, et al. Psychoneuroendocrine modulation of regulatory T lymphocyte system: in vivo and in vitro effects of the pineal immunomodulating hormone melatonin. In Vivo. 2010;24:787–789.
147. Bizzarri M, Proietti S, Cucina A, et al. Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer: a review. Expert Opin Ther Targets. 2013;17:1483-1496.
148. Jaigirdar SA, MacLeod MK. Development and function of protective and pathologic memory CD4 T cells. Front Immunol. 2015;6:456.
149. Pedrosa AM, Weinlich R, Mognol GP, et al. Melatonin protects CD4+ T cells from activation-induced cell death by blocking NFAT-mediated CD95 ligand upregulation. J Immunol. 2010;184:3487–3494.
150. Drazen DL, Bilu D, Bilbo SD, et al. Melatonin enhancement of splenocyte proliferation is attenuated by luzindole, a melatonin receptor antagonist. Am J Physiol Regul Integr Comp Physiol. 2001;280:R1476–R1482.
151. Lardone PJ, Carrillo-Vico A, Molinero P, et al. A novel interplay between membrane and nuclear melatonin receptors in human lymphocytes: significance in IL-2 production. Cell Mol Life Sci. 2009;66:516–525.
152. Min KJ, Jang JH, Kwon TK. Inhibitory effects of melatonin on the lipopolysaccharide-induced CC chemokine expression in BV2 murine microglial cells are mediated by suppression of Akt-induced NF-kappaB and STAT/GAS activity. J Pineal Res. 2012;52:296–304.
153. Ivanov II, McKenzie BS, Zhou L, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126:1121–1133.
154. Yang XO, Pappu BP, Nurieva R, et al. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity. 2008;28:29–39.
155. Yu X, Rollins D, Ruhn KA, et al. TH17 cell differentiation is regulated by the circadian clock. Science. 2013;2013:727–730.
156. Lau WW, Ng JK, Lee MM, et al. Interleukin-6 autocrine signaling mediates melatonin MT(1/2) receptor-induced STAT3 Tyr(705) phosphorylation. J Pineal Res. 2012;2012:477–489.
157. Ren W, Yin J, Xiao H, et al. Intestinal microbiota-derived GABA mediates interleukin-17 expression during enterotoxigenic Escherichia coli infection. Front Immunol. 2016;7:685.
158. Sanchez DI, Gonzalez-Fernandez B, San-Miguel B, et al. Melatonin prevents deregulation of the sphingosine kinase/sphingosine 1-phosphate signaling pathway in a mouse model of diethylnitrosamine-induced hepatocellular carcinoma. J Pineal Res. 2017;62. doi: 10.1111/jpi.12369.
159. Lin C, Chao H, Li Z, et al. Melatonin attenuates traumatic brain injury-induced inflammation: a possible role for mitophagy. J Pineal Res. 2016;61:177–186.
160. Wolfler A, Schauenstein K, Liebmann PM. Lack of calmodulin antagonism of melatonin in T-lymphocyte activation. Life Sci. 1998;63:835–842.
161. Anonymous. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837–853.
162. Gaglia JL, Shapiro AM, Weir GC. Islet transplantation: progress and challenge. Arch Med Res. 2005;36:273–280.
163. Balamurugan AN, Bottino R, Giannoukakis N, et al. Prospective and challenges of islet transplantation for the therapy of autoimmune diabetes. Pancreas. 2006;32:231–243.
164. Aoki CA, Borchers AT, Ridgway WM, et al. NOD mice and autoimmunity. Autoimmun Rev. 2005;4:373–379.
165. Lin GJ, Huang SH, Chen YW, et al. Melatonin prolongs islet graft survival in diabetic NOD mice. J Pineal Res. 2009;47:284–292.
166. Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med. 2008;358:929–939.
167. Crispin JC, Liossis SN, Kis-Toth K, et al. Pathogenesis of human systemic lupus erythematosus: recent advances. Trends Mol Med. 2010;2010:47–57.
168. Gomez D, Correa PA, Gomez LM, et al. Th1/Th2 cytokines in patients with systemic lupus erythematosus: is tumor necrosis factor alpha protective? Semin Arthritis Rheum. 2004;33:404–413.
169. Wong CK, Ho CY, Li EK, et al. Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus. Lupus. 2000;9:589–593.
170. Ouyang H, Shi Y, Liu Z, et al. Increased interleukin9 and CD4+IL-9+ T cells in patients with systemic lupus erythematosus. Mol Med Rep. 2013;2013:1031–1037.
171. Andrews BS, Eisenberg RA, Theofilopoulos AN, et al. Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med. 1978;148:1198–1215.
172. Hang L, Theofilopoulos AN, Dixon FJ. A spontaneous rheumatoid arthritis-like disease in MRL/l mice. J Exp Med. 1982;155:1690–1701.
173. Watanabe-Fukunaga R, Brannan CI, Copeland NG, et al. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992;356:314–317.
174. Jimenez-Caliani AJ, Jimenez-Jorge S, Molinero P, et al. Sex-dependent effect of melatonin on systemic erythematosus lupus developed in Mrl/Mpj-Faslpr mice: it ameliorates the disease course in females, whereas it exacerbates it in males. Endocrinology. 2006;2006:1717–1724.
175. Milo R, Kahana E. Multiple sclerosis: geoepidemiology, genetics and the environment. Autoimmun Rev. 2010;9:A387-A394.
176. Frohman EM, Racke MK, Raine CS. Multiple sclerosis–the plaque and its pathogenesis. N Engl J Med. 2006;354:942–955.
177. Zamvil SS, Steinman L. The T lymphocyte in experimental allergic encephalomyelitis. Annu Rev Immunol. 1990;8:579–621.
178. Kebir H, Kreymborg K, Ifergan I, et al. Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med. 2007;2007:1173–1175.
179. Langrish CL, Chen Y, Blumenschein WM, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005;2005:233–240.
180. Brazao V, Santello FH, Filipin Mdel V, et al. Immunoregulatory actions of melatonin and zinc during chronic Trypanosoma cruzi infection. J Pineal Res. 2015;58:210–218.
181. Hu W, Ma Z, Jiang S, et al. Melatonin: the dawning of a treatment for fibrosis? J Pineal Res. 2016;60:121–131.
182. Kleszczynski K, Zillikens D, Fischer TW. Melatonin enhances mitochondrial ATP synthesis reduces reactive oxygen species formation, and mediates translocation of the nuclear erythroid 2-related factor 2 resulting in activation of phase-2 antioxidant enzymes (γ-GCS, HO-1, NQO1) in ultraviolet radiation-treated normal human epidermal keratinocytes (NHEK). J Pineal Res. 2016;61:187–197.
183. Calvo JR, Gonzalez-Yanes C, Maldonado MD. The role of melatonin in the cells of the innate immunity: a review. J Pineal Res. 2013;55:103–120.
184. Sun CK, Lee FY, Kao YH, et al. Systemic combined melatonin-mitochondria treatment improves acute respiratory distress syndrome in the rat. J Pineal Res. 2015;58:137–150.
185. Volt H, Garcia JA, Doerrier C, et al. Same molecule but different expression: aging and sepsis trigger NLRP3 inflammasome activation, a target of melatonin. J Pineal Res. 2016;60:193–205.
186. Godfrey DI, Uldrich AP, McCluskey J, et al. The burgeoning family of unconventional T cells. Nat Immunol. 2015;16:1114–1123.
187. Ren WK, Liu G, Yin J, et al. Amino-acid transporters in T-cell activation and differentiation. Cell Death Dis. 2016;7. doi: 10.1038/cddis.2016.222.
188. Reiter RJ, Tan DX, Korkmaz A, et al. Obesity and metabolic syndrome: association with chronodisruption, sleep deprivation and melatonin suppression. Ann Med. 2012;44:564–577.
189. Chuffa LG, Lupi Junior LA, Seiva FR, et al. Quantitative proteomic profiling reveals that diverse metabolic pathways are influenced by melatonin in an in vivo model of ovarian carcinoma. J Proteome Res. 2016;15:3872–3882.