Epigenetic patterns associated with the immune dysregulation that accompanies psychosocial distress

Brain, Behavior, and Immunity

Volumn 25, Issue 5, 2011, Pages 830-839

  Mathews, Herbert L ^a   Konley, Teresa ^a   Kosik, Kelly Loster ^a   Krukowski, Karen ^a   Eddy, Justin ^a   Albuquerque, Kevin ^a   Janusek, Linda Witek ^b  

^a LOYOLA UNIVERSITY CHICAGO   (United States)

^b LOYOLA UNIVERSITY CHICAGO   (United States)

Author keywords

Epigenetic; Histone acetylation and phosphorylation; Interferon gamma; NK cell activity

Indexed keywords

GAMMA INTERFERON; HISTONE H3; HISTONE H4;

ACETYLATION; ADULT; AGED; ANXIETY DISORDER; ARTICLE; BREAST CANCER; CANCER STAGING; CLINICAL ARTICLE; CONTROLLED STUDY; DISTRESS SYNDROME; EARLY CANCER; EPIGENETICS; FEMALE; HUMAN; HUMAN CELL; IMMUNE DYSREGULATION; INTERFERON PRODUCTION; MOOD DISORDER; NATURAL KILLER CELL; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SOCIAL PSYCHOLOGY;

ADULT; AGED; BREAST NEOPLASMS; CARCINOMA, INTRADUCTAL, NONINFILTRATING; CYTOKINES; EPIGENESIS, GENETIC; FEMALE; FLOW CYTOMETRY; HUMANS; IMMUNE SYSTEM DISEASES; INTERFERON-GAMMA; KILLER CELLS, NATURAL; LYMPHOCYTES; MIDDLE AGED; PSYCHOLOGICAL TESTS; STRESS, PSYCHOLOGICAL;

EID: 79957922071     PISSN: 08891591     EISSN: 10902139     Source Type: Journal    
DOI: 10.1016/j.bbi.2010.12.002     Document Type: Article

References (98)

1. Andersen B.L., Farrar W.B., Golden-Kreutz D., Kutz L.A., Maccallum R., Courtney M.E., Glaser R. Stress and immune responses after surgical treatment for regional breast cancer. J. Natl. Cancer Inst. 1998, 90:30-36.
2. Andersen B.L., Farrar W.B., Golden-Kreutz D.M., Glaser R., Emery C.F., Crespin T.R., Shapiro C.L., Carson W.E. Psychological, behavioral, and immune changes after a psychological intervention: a clinical trial. J. Clin. Oncol. 2004, 22:3570-3580.
3. Arbibe L., Kim D.W., Batsche E., Pedron T., Mateescu B., Muchardt C., Parsot C., Sansonetti P.J. An injected bacterial effector targets chromatin access for transcription factor NF-kappaB to alter transcription of host genes involved in immune responses. Nat. Immunol. 2007, 8:47-56.
4. Avni O., Lee D., Macian F., Szabo S.J., Glimcher L.H., Rao A. T(H) cell differentiation is accompanied by dynamic changes in histone acetylation of cytokine genes. Nat. Immunol. 2002, 3:643-651.
5. Avraham R., Ben-Eliyahu S. Neuroendocrine regulation of cancer progression: II. Immunological mechanisms, clinical relevance, and prophylactic measures. Psychoneuroimmunology 2007, 251-265. Elsevier Academic Press, Burlington, MA. fourth ed. R. Ader (Ed.).
6. Babichuk C.K., Duggan B.L., Bleackley R.C. In vivo regulation of murine granzyme B gene transcription in activated primary T cells. J. Biol. Chem. 1996, 271:16485-16493.
7. Barnes P.J. Anti-inflammatory mechanisms of glucocorticoids. Biochem. Soc. Trans. 1995, 23:940-945.
8. Barnes P.J. Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin. Sci. (Lond.) 1998, 94:557-572.
9. Beno D.W., Stover A.G., Mathews H.L. Growth inhibition of Candida albicans hyphae by CD8+ lymphocytes. J. Immunol. 1995, 154:5273-5281.
10. Bilang-Bleuel A., Ulbricht S., Chandramohan Y., De Carli S., Droste S.K., Reul J.M. Psychological stress increases histone H3 phosphorylation in adult dentate gyrus granule neurons: involvement in a glucocorticoid receptor-dependent behavioural response. Eur. J. Neurosci. 2005, 22:1691-1700.
11. Biondi M. Effects of stress on immune functions: an overview. Psychoneuroimmunology 2001, 189-226. Academic Press, New York. third ed. R. Ader, N. Cohen (Eds.).
12. Bjornsson H.T., Daniele Fallin M., Feinberg A.P. An integrated epigenetic and genetic approach to common human disease. Trends Genet. 2004, 20:350-358.
13. Chandramohan Y., Droste S.K., Arthur J.S., Reul J.M. The forced swimming-induced behavioural immobility response involves histone H3 phospho-acetylation and c-Fos induction in dentate gyrus granule neurons via activation of the N-methyl-d-aspartate/extracellular signal-regulated kinase/mitogen- and stress-activated kinase signalling pathway. Eur. J. Neurosci. 2008, 27:2701-2713.
14. Chandramohan Y., Droste S.K., Reul J.M. Novelty stress induces phospho-acetylation of histone H3 in rat dentate gyrus granule neurons through coincident signalling via the N-methyl-d-aspartate receptor and the glucocorticoid receptor: relevance for c-fos induction. J. Neurochem. 2007, 101:815-828.
15. Chrousos G.P. The stress response and immune function: clinical implications. The 1999 Novera H. Spector Lecture. Ann. NY Acad. Sci. 2000, 917:38-67.
16. Chrousos G.P., Gold P.W. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA 1992, 267:1244-1252.
17. Cippitelli M., Sica A., Viggiano V., Ye J., Ghosh P., Birrer M.J., Young H.A. Negative transcriptional regulation of the interferon-gamma promoter by glucocorticoids and dominant negative mutants of c-Jun. J. Biol. Chem. 1995, 270:12548-12556.
18. Cohen S., Williamson G.M. Perceived stress in a probability sample of the United States. The Social Psychology of Health 1988, 31-67. Sage Publications. S. Spacapan, S. Oskamp (Eds.).
19. Cole S.W., Hawkley L.C., Arevalo J.M., Sung C.Y., Rose R.M., Cacioppo J.T. Social regulation of gene expression in human leukocytes. Genome Biol. 2007, 8:R189.
20. Cuddapah S., Barski A., Zhao K. Epigenomics of T cell activation, differentiation, and memory. Curr. Opin. Immunol. 2010, 22:341-347.
21. Decker D., Schondorf M., Bidlingmaier F., Hirner A., Von Ruecker A.A. Surgical stress induces a shift in the type-1/type-2 T-helper cell balance, suggesting down-regulation of cell-mediated and up-regulation of antibody-mediated immunity commensurate to the trauma. Surgery 1996, 119:316-325.
22. Dighe A.S., Richards E., Old L.J., Schreiber R.D. Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity 1994, 1:447-456.
23. Edgar L., Rosberger Z., Nowlis D. Coping with cancer during the first year after diagnosis. Assessment and intervention. Cancer 1992, 69:817-828.
24. Espada J., Esteller M. Epigenetic control of nuclear architecture. Cell. Mol. Life Sci. 2007, 64:449-457.
25. Esterling B.A., Kiecolt-Glaser J.K., Bodnar J.C., Glaser R. Chronic stress, social support, and persistent alterations in the natural killer cell response to cytokines in older adults. Health Psychol. 1994, 13:291-298.
26. Fawzy F.I., Kemeny M.E., Fawzy N.W., Elashoff R., Morton D., Cousins N., Fahey J.L. A structured psychiatric intervention for cancer patients. II. Changes over time in immunological measures. Arch. Gen. Psychiatry 1990, 47:729-735.
27. Ganz P.A., Coscarelli A., Fred C., Kahn B., Polinsky M.L., Petersen L. Breast cancer survivors: psychosocial concerns and quality of life. Breast Cancer Res. Treat. 1996, 38:183-199.
28. Glaser R., Kiecolt-Glaser J.K. Stress-induced immune dysfunction: implications for health. Nat. Rev. Immunol. 2005, 5:243-251.
29. Glaser R., Rice J., Speicher C.E., Stout J.C., Kiecolt-Glaser J.K. Stress depresses interferon production by leukocytes concomitant with a decrease in natural killer cell activity. Behav. Neurosci. 1986, 100:675-678.
30. Govind C.K., Zhang F., Qiu H., Hofmeyer K., Hinnebusch A.G. Gcn5 promotes acetylation, eviction, and methylation of nucleosomes in transcribed coding regions. Mol. Cell 2007, 25:31-42.
31. Henikoff S., Ahmad K. Assembly of variant histones into chromatin. Annu. Rev. Cell Dev. Biol. 2005, 21:133-153.
32. Homburger J.A., Meiler S.E. Anesthesia drugs, immunity, and long-term outcome. Curr. Opin. Anaesthesiol. 2006, 19:423-428.
33. Hunter R.G., Mccarthy K.J., Milne T.A., Pfaff D.W., Mcewen B.S. Regulation of hippocampal H3 histone methylation by acute and chronic stress. Proc. Natl. Acad. Sci. USA 2009, 106:20912-20917.
34. Ito K., Barnes P.J., Adcock I.M. Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1beta-induced histone H4 acetylation on lysines 8 and 12. Mol. Cell. Biol. 2000, 20:6891-6903.
35. Ito K., Yamamura S., Essilfie-Quaye S., Cosio B., Ito M., Barnes P.J., Adcock I.M. Histone deacetylase 2-mediated deacetylation of the glucocorticoid receptor enables NF-kappaB suppression. J. Exp. Med. 2006, 203:7-13.
36. Kagi D., Ledermann B., Burki K., Seiler P., Odermatt B., Olsen K.J., Podack E.R., Zinkernagel R.M., Hengartner H. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature 1994, 369:31-37.
37. Kagoshima M., Ito K., Cosio B., Adcock I.M. Glucocorticoid suppression of nuclear factor-kappa B: a role for histone modifications. Biochem. Soc. Trans. 2003, 31:60-65.
38. Kagoshima M., Wilcke T., Ito K., Tsaprouni L., Barnes P.J., Punchard N., Adcock I.M. Glucocorticoid-mediated transrepression is regulated by histone acetylation and DNA methylation. Eur. J. Pharmacol. 2001, 429:327-334.
39. Kaplan D.H., Shankaran V., Dighe A.S., Stockert E., Aguet M., Old L.J., Schreiber R.D. Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc. Natl. Acad. Sci. USA 1998, 95:7556-7561.
40. Kemeny M.E., Schedlowski M. Understanding the interaction between psychosocial stress and immune-related diseases: a stepwise progression. Brain Behav. Immun. 2007, 21:1009-1018.
41. Kiecolt-Glaser J.K., Dura J.R., Speicher C.E., Trask O.J., Glaser R. Spousal caregivers of dementia victims: longitudinal changes in immunity and health. Psychosom. Med. 1991, 53:345-362.
42. Kiecolt-Glaser J.K., Glaser R., Gravenstein S., Malarkey W.B., Sheridan J. Chronic stress alters the immune response to influenza virus vaccine in older adults. Proc. Natl. Acad. Sci. USA 1996, 93:3043-3047.
43. Kiecolt-Glaser J.K., Glaser R., Shuttleworth E.C., Dyer C.S., Ogrocki P., Speicher C.E. Chronic stress and immunity in family caregivers of Alzheimer's disease victims. Psychosom. Med. 1987, 49:523-535.
44. Kim H.G., Lee K.W., Cho Y.Y., Kang N.J., Oh S.M., Bode A.M., Dong Z. Mitogen- and stress-activated kinase 1-mediated histone H3 phosphorylation is crucial for cell transformation. Cancer Res. 2008, 68:2538-2547.
45. Koda K., Saito N., Takiguchi N., Oda K., Nunomura M., Nakajima N. Preoperative natural killer cell activity: correlation with distant metastases in curatively research colorectal carcinomas. Int. Surg. 1997, 82:190-193.
46. Koltun W.A., Bloomer M.M., Tilberg A.F., Seaton J.F., Ilahi O., Rung G., Gifford R.M., Kauffman G.L. Awake epidural anesthesia is associated with improved natural killer cell cytotoxicity and a reduced stress response. Am. J. Surg. 1996, 171:68-72. discussion 72-73.
47. Krukowski, K., Eddy, J., Kosik, K.L., Konley, T., Janusek, L.W., Mathews, H.L., in press. Glucocorticoid dysregulation of natural killer cell function through epigenetic modification. Brain Behav. Immun. [Epub ahead of print], PMID: 20656012.
48. Kutza J., Gratz I., Afshar M., Murasko D.M. The effects of general anesthesia and surgery on basal and interferon stimulated natural killer cell activity of humans. Anesth. Analg. 1997, 85:918-923.
49. Larson M.R., Duberstein P.R., Talbot N.L., Caldwell C., Moynihan J.A. A presurgical psychosocial intervention for breast cancer patients. Psychological distress and the immune response. J. Psychosom. Res. 2000, 48:187-194.
50. Lieb J.D., Clarke N.D. Control of transcription through intragenic patterns of nucleosome composition. Cell 2005, 123:1187-1190.
51. Lu Q., Wu A., Ray D., Deng C., Attwood J., Hanash S., Pipkin M., Lichtenheld M., Richardson B. DNA methylation and chromatin structure regulate T cell perforin gene expression. J. Immunol. 2003, 170:5124-5132.
52. Lutgendorf S., Costanzo E., Siegel S. Psychosocial influences in oncology: an expanded model of biobehavioral mechanisms. Psychoneuroimmunology 2007, 869-895. Elsevier Academic Press, Burlington, MA. fourth ed. R. Ader (Ed.).
53. Maes M., Lin A.H., Delmeire L., Van Gastel A., Kenis G., De Jongh R., Bosmans E. Elevated serum interleukin-6 (IL-6) and IL-6 receptor concentrations in posttraumatic stress disorder following accidental man-made traumatic events. Biol. Psychiatry 1999, 45:833-839.
54. Marshall G.D., Agarwal S.K., Lloyd C., Cohen L., Henninger E.M., Morris G.J. Cytokine dysregulation associated with exam stress in healthy medical students. Brain Behav. Immun. 1998, 12:297-307.
55. Martino D.J., Prescott S.L. Silent mysteries: epigenetic paradigms could hold the key to conquering the epidemic of allergy and immune disease. Allergy 2010, 65:7-15.
56. Matthews J.G., Ito K., Barnes P.J., Adcock I.M. Defective glucocorticoid receptor nuclear translocation and altered histone acetylation patterns in glucocorticoid-resistant patients. J. Allergy Clin. Immunol. 2004, 113:1100-1108.
57. Mcnair, D.M., Lorr, M., Droppleman, L.F., 1992. Manual for the Profile of Mood States, EdiTs, San Diego.
58. Miller G.E., Chen E., Sze J., Marin T., Arevalo J.M., Doll R., Ma R., Cole S.W. A functional genomic fingerprint of chronic stress in humans: blunted glucocorticoid and increased NF-kappaB signaling. Biol. Psychiatry 2008, 64:266-272.
59. Mishra N., Brown D.R., Olorenshaw I.M., Kammer G.M. Trichostatin A reverses skewed expression of CD154, interleukin-10, and interferon-gamma gene and protein expression in lupus T cells. Proc. Natl. Acad. Sci. USA 2001, 98:2628-2633.
60. Mokart D., Capo C., Blache J.L., Delpero J.R., Houvenaeghel G., Martin C., Mege J.L. Early postoperative compensatory anti-inflammatory response syndrome is associated with septic complications after major surgical trauma in patients with cancer. Br. J. Surg. 2002, 89:1450-1456.
61. Monroe S., Kelley J. Measurement of stress appraisal. Measuring Stress: A Guide for Health and Social Scientists 1995, 122-147. Oxford University Press, New York. S. Cohen, R.C. Kessler, L. Underwood Gordon (Eds.).
62. Muegge K., Young H., Ruscetti F., Mikovits J. Epigenetic control during lymphoid development and immune responses: aberrant regulation, viruses, and cancer. Ann. NY Acad. Sci. 2003, 983:55-70.
63. Nagabhushan M., Mathews H.L., Witek-Janusek L. Aberrant nuclear expression of ap-1 and nfkb in lymphocytes of women stressed by the experience of breast biopsy. Brain Behav. Immun. 2001, 15:78-84.
64. National Cancer Institute, 1997. Cancer Facts: 1996. Washington, DC.
65. Parra M., Mahmoudi T., Verdin E. Myosin phosphatase dephosphorylates HDAC7, controls its nucleocytoplasmic shuttling, and inhibits apoptosis in thymocytes. Genes Dev. 2007, 21:638-643.
66. Plesko M.M., Hargrove J.L., Granner D.K., Chalkley R. Inhibition by sodium butyrate of enzyme induction by glucocorticoids and dibutyryl cyclic AMP. A role for the rapid form of histone acetylation. J. Biol. Chem. 1983, 258:13738-13744.
67. Pollock R.E., Lotzova E., Stanford S.D. Mechanism of surgical stress impairment of human perioperative natural killer cell cytotoxicity. Arch. Surg. 1991, 126:338-342.
68. Reinke H., Horz W. Histones are first hyperacetylated and then lose contact with the activated PHO5 promoter. Mol. Cell 2003, 11:1599-1607.
69. Saccani S., Pantano S., Natoli G. p38-Dependent marking of inflammatory genes for increased NF-kappa B recruitment. Nat. Immunol. 2002, 3:69-75.
70. Sachs G., Rasoul-Rockenschaub S., Aschauer H., Spiess K., Gober I., Staffen A., Zielinski C. Lytic effector cell activity and major depressive disorder in patients with breast cancer: a prospective study. J. Neuroimmunol. 1995, 59:83-89.
71. Schotta G., Lachner M., Peters A.H., Jenuwein T. The indexing potential of histone lysine methylation. Novartis Found. Symp. 2004, 259:22-37. discussion 37-47, 163-169.
72. Segerstrom S.C., Miller G.E. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol. Bull. 2004, 130:601-630.
73. Seki N., Hayakawa Y., Brooks A.D., Wine J., Wiltrout R.H., Yagita H., Tanner J.E., Smyth M.J., Sayers T.J. Tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis is an important endogenous mechanism for resistance to liver metastases in murine renal cancer. Cancer Res. 2003, 63:207-213.
74. Shahbazian M.D., Grunstein M. Functions of site-specific histone acetylation and deacetylation. Annu. Rev. Biochem. 2007, 76:75-100.
75. Shakhar G., Ben-Eliyahu S. Potential prophylactic measures against postoperative immunosuppression: could they reduce recurrence rates in oncological patients?. Ann. Surg. Oncol. 2003, 10:972-992.
76. Shapiro S.L., Lopez A.M., Schwartz G.E., Bootzin R., Figueredo A.J., Braden C.J., Kurker S.F. Quality of life and breast cancer: relationship to psychosocial variables. J. Clin. Psychol. 2001, 57:501-519.
77. Smyth M.J., Kelly J.M., Baxter A.G., Korner H., Sedgwick J.D. An essential role for tumor necrosis factor in natural killer cell-mediated tumor rejection in the peritoneum. J. Exp. Med. 1998, 188:1611-1619.
78. Smyth M.J., Thia K.Y., Cretney E., Kelly J.M., Snook M.B., Forbes C.A., Scalzo A.A. Perforin is a major contributor to NK cell control of tumor metastasis. J. Immunol. 1999, 162:6658-6662.
79. Smyth M.J., Wallace M.E., Nutt S.L., Yagita H., Godfrey D.I., Hayakawa Y. Sequential activation of NKT cells and NK cells provides effective innate immunotherapy of cancer. J. Exp. Med. 2005, 201:1973-1985.
80. Spielberger C.D., Gorsuch R.C., Lushene R.E., Vagg P.R., Jacobs G.A. Manual for the State-Trait Anxiety Inventory 1970, Mind Garden Inc., Menlo Park, p. 457.
81. Spies C.D., Von Dossow V., Eggers V., Jetschmann G., El-Hilali R., Egert J., Fischer M., Schroder T., Hoflich C., Sinha P., Paschen C., Mirsalim P., Brunsch R., Hopf J., Marks C., Wernecke K.D., Pragst F., Ehrenreich H., Muller C., Tonnesen H., Oelkers W., Rohde W., Stein C., Kox W.J. Altered cell-mediated immunity and increased postoperative infection rate in long-term alcoholic patients. Anesthesiology 2004, 100:1088-1100.
82. Street S.E., Cretney E., Smyth M.J. Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 2001, 97:192-197.
83. Thomas R.M., Gao L., Wells A.D. Signals from CD28 induce stable epigenetic modification of the IL-2 promoter. J. Immunol. 2005, 174:4639-4646.
84. Thornton L.M., Andersen B.L., Crespin T.R., Carson W.E. Individual trajectories in stress covary with immunity during recovery from cancer diagnosis and treatments. Brain Behav. Immun. 2007, 21:185-194.
85. Tsankova N.M., Berton O., Renthal W., Kumar A., Neve R.L., Nestler E.J. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat. Neurosci. 2006, 9:519-525.
86. Tsaprouni L.G., Ito K., Punchard N., Adcock I.M. Triamcinolone acetonide and dexamethasome suppress TNF-alpha-induced histone H4 acetylation on lysine residues 8 and 12 in mononuclear cells. Ann. NY Acad. Sci. 2002, 973:481-483.
87. Van Den Broek M.E., Kagi D., Ossendorp F., Toes R., Vamvakas S., Lutz W.K., Melief C.J., Zinkernagel R.M., Hengartner H. Decreased tumor surveillance in perforin-deficient mice. J. Exp. Med. 1996, 184:1781-1790.
88. Wallace M.E., Smyth M.J. The role of natural killer cells in tumor control - effectors and regulators of adaptive immunity. Springer Semin. Immunopathol. 2005, 27:49-64.
89. Whelan R.L., Franklin M., Holubar S.D., Donahue J., Fowler R., Munger C., Doorman J., Balli J.E., Glass J., Gonzalez J.J., Bessler M., Xie H., Treat M. Postoperative cell mediated immune response is better preserved after laparoscopic vs. open colorectal resection in humans. Surg. Endosc. 2003, 17:972-978.
90. Wichmann M.W., Meyer G., Adam M., Hochtlen-Vollmar W., Angele M.K., Schalhorn A., Wilkowski R., Muller C., Schildberg F.W. Detrimental immunologic effects of preoperative chemoradiotherapy in advanced rectal cancer. Dis. Colon Rectum 2003, 46:875-887.
91. Wilkinson M.B., Xiao G., Kumar A., Laplant Q., Renthal W., Sikder D., Kodadek T.J., Nestler E.J. Imipramine treatment and resiliency exhibit similar chromatin regulation in the mouse nucleus accumbens in depression models. J. Neurosci. 2009, 29:7820-7832.
92. Witek-Janusek L., Albuquerque K., Chroniak K.R., Chroniak C., Durazo-Arvizu R., Mathews H.L. Effect of mindfulness based stress reduction on immune function, quality of life and coping in women newly diagnosed with early stage breast cancer. Brain Behav. Immun. 2008, 22:969-981.
93. Witek-Janusek L., Gabram S., Mathews H.L. Psychologic stress, reduced NK cell activity, and cytokine dysregulation in women experiencing diagnostic breast biopsy. Psychoneuroendocrinology 2007, 32:22-35.
94. Witek-Janusek L., Mathews H.L. Differential effects of glucocorticoids on colony stimulating factors produced by neonatal mononuclear cells. Pediatr. Res. 1999, 45:224-229.
95. Witek-Janusek L., Mathews H.L. Stress, immunity, and health outcomes. Handbook of Stress, Coping, and Health: Implications for Nursing Research, Theory, and Practice 2000, 47-67. Sage Publications, Thousand Oaks. first ed. V. Rice (Ed.).
96. Wrona D. Neural-immune interactions: an integrative view of the bidirectional relationship between the brain and immune systems. J. Neuroimmunol. 2006, 172:38-58.
97. Yamamura Y., Rodriguez N., Schwartz A., Eylar E., Bagwell B., Yano N. A new flow cytometric method for quantitative assessment of lymphocyte mitogenic potentials. Cell. Mol. Biol. 1995, 41:S121-S132.
98. Zhang T.Y., Meaney M.J. Epigenetics and the environmental regulation of the genome and its function. Annu. Rev. Psychol. 2010, 61(439-466):C431-C433.