Suppressive effects of androgens on the immune system

Cellular Immunology

Volumn 294, Issue 2, 2015, Pages 87-94

  Trigunaite, Abhishek ^a   Dimo, Joana ^a   Jørgensen, Trine N ^a  

^a LERNER RESEARCH INSTITUTE   (United States)

Author keywords

Adaptive immunity; Androgen; Androgen receptor; Autoimmunity; Cancer; Innate immunity; Sex bias; Testosterone

Indexed keywords

TESTOSTERONE;

ADAPTIVE IMMUNITY; ANTIBODY RESPONSE; ARTICLE; AUTOIMMUNITY; B LYMPHOCYTE; CELL MATURATION; CELL SPECIFICITY; CONVENTIONAL DENDRITIC CELL; DENDRITIC CELL; DOWN REGULATION; EFFECTOR CELL; HUMAN; IMMUNE DYSREGULATION; IMMUNOREACTIVITY; INNATE IMMUNITY; LYMPHOCYTE DIFFERENTIATION; MACROPHAGE; MONOCYTE; NEOPLASM; NEUTROPHIL; NONHUMAN; PLASMACYTOID DENDRITIC CELL; POPULATION; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION; TH1 CELL; TH2 CELL; TUMOR IMMUNITY; CELL DIFFERENTIATION; CYTOLOGY; FEMALE; IMMUNOLOGICAL TOLERANCE; IMMUNOLOGY; MALE; PHYSIOLOGY; SEXUAL DEVELOPMENT; T LYMPHOCYTE;

ADAPTIVE IMMUNITY; B-LYMPHOCYTES; CELL DIFFERENTIATION; DENDRITIC CELLS; DOWN-REGULATION; FEMALE; HUMANS; IMMUNE TOLERANCE; IMMUNITY, INNATE; MACROPHAGES; MALE; SEX CHARACTERISTICS; T-LYMPHOCYTES; TESTOSTERONE;

EID: 84930903038     PISSN: 00088749     EISSN: 10902163     Source Type: Journal    
DOI: 10.1016/j.cellimm.2015.02.004     Document Type: Article

References (141)

1. E. Ainbender, R.B. Weisinger, M. Hevizy, H.L. Hodes, Difference in the immunoglobulin class of polioantibody in the serum of men and women, J. Immunol. 101 (1968) 92-98.
2. M.J. Rowley, I.R. Mackay, Measurement of antibody-producing capacity in man. I. The normal response to flagellin from Salmonella adelaide, Clin. Exp. Immunol. 5 (1969) 407-418.
3. E. Der, J. Dimo, A. Trigunaite, J. Jones, T.N. Jorgensen, Gr1+ cells suppress Tdependent antibody responses in (NZB × NZW)F1 male mice through inhibition of T follicular helper cells and germinal center formation, J. Immunol. 192 (2014) 1570-1576.
4. D. Fairweather, N.R. Rose, Women and autoimmune diseases, Emerg. Infect. Dis. 10 (2004) 2005-2011.
5. C.C. Whitacre, Sex differences in autoimmune disease, Nat. Immunol. 2 (2001) 777-780.
6. Y.T. Koh, A. Gray, S.A. Higgins, B. Hubby, W.M. Kast, Androgen ablation augments prostate cancer vaccine immunogenicity only when applied after immunization, Prostate 69 (2009) 571-584.
7. J.P. Wang, L. Zhang, R.F. Madera, M. Woda, D.H. Libraty, Plasmacytoid dendritic cell interferon-alpha production to R-848 stimulation is decreased in male infants, BMC Immunol. 13 (2012) 35.
8. I.H. Kocar, Z. Yesilova, M. Ozata, M. Turan, A. Sengul, I. Ozdemir, The effect of testosterone replacement treatment on immunological features of patients with Klinefelter's syndrome, Clin. Exp. Immunol. 121 (2000) 448-452.
9. W. Muller, T.G. Groothuis, A. Kasprzik, C. Dijkstra, R.V. Alatalo, H. Siitari, Prenatal androgen exposure modulates cellular and humoral immune function of black-headed gull chicks, Proc. Biol. Sci. 272 (2005) 1971-1977.
10. K.J. Navara, G.E. Hill, M.T. Mendonca, Variable effects of yolk androgens on growth, survival, and immunity in eastern bluebird nestlings, Physiol. Biochem. Zool. 78 (2005) 570-578.
11. M.I. Sandell, M. Tobler, D. Hasselquist, Yolk androgens and the development of avian immunity: an experiment in jackdaws (Corvus monedula), J. Exp. Biol. 212 (2009) 815-822.
12. L.J. Seivwright, S.M. Redpath, F. Mougeot, F. Leckie, P.J. Hudson, Interactions between intrinsic and extrinsic mechanisms in a cyclic species: testosterone increases parasite infection in red grouse, Proc. Biol. Sci. 272 (2005) 2299-2304.
13. S.G. Clairardin, C.A. Barnett, S.K. Sakaluk, C.F. Thompson, Experimentally increased in ovo testosterone leads to increased plasma bactericidal activity and decreased cutaneous immune response in nestling house wrens, J. Exp. Biol. 214 (2011) 2778-2782.
14. D. Perry, A. Sang, Y. Yin, Y.Y. Zheng, L. Morel, Murine models of systemic lupus erythematosus, J. Biomed. Biotechnol. 2011 (2011) 271694.
15. J.R. Roubinian, N. Talal, J.S. Greenspan, J.R. Goodman, P.K. Siiteri, Effect of castration and sex hormone treatment on survival, anti-nucleic acid antibodies, and glomerulonephritis in NZB/NZW F1 mice, J. Exp. Med. 147 (1978) 1568-1583.
16. J.R. Roubinian, R. Papoian, N. Talal, Androgenic hormones modulate autoantibody responses and improve survival in murine lupus, J. Clin. Invest. 59 (1977) 1066-1070.
17. M.O. Ziehn, A.A. Avedisian, S.M. Dervin, E.A. Umeda, T.J. O'Dell, R.R. Voskuhl, Therapeutic testosterone administration preserves excitatory synaptic transmission in the hippocampus during autoimmune demyelinating disease, J. Neurosci. 32 (2012) 12312-12324.
18. M. Pikwer, A. Giwercman, U. Bergstrom, J.A. Nilsson, L.T. Jacobsson, C. Turesson, Association between testosterone levels and risk of future rheumatoid arthritis in men: a population-based case-control study, Ann. Rheum. Dis. 73 (2014) 573-579.
19. R.C. Keith, J. Sokolove, B.L. Edelman, L. Lahey, E.F. Redente, V.M. Holers, S. Sakaguchi, W.H. Robinson, D.W. Riches, Testosterone is protective in the sexually dimorphic development of arthritis and lung disease in SKG mice, Arthritis Rheum. 65 (2013) 1487-1493.
20. N.L. Sicotte, B.S. Giesser, V. Tandon, R. Klutch, B. Steiner, A.E. Drain, D.W. Shattuck, L. Hull, H.J. Wang, R.M. Elashoff, R.S. Swerdloff, R.R. Voskuhl, Testosterone treatment in multiple sclerosis: a pilot study, Arch. Neurol. 64 (2007) 683-688.
21. C. Gordon, D.J. Wallace, S. Shinada, K.C. Kalunian, L. Forbess, G.D. Braunstein, M.H. Weisman, Testosterone patches in the management of patients with mild/moderate systemic lupus erythematosus, Rheumatology (Oxford) 47 (2008) 334-338.
22. M.S. Pearce, L. Parker, Childhood cancer registrations in the developing world: still more boys than girls, Int. J. Cancer 91 (2001) 402-406.
23. R.A. Cartwright, K.A. Gurney, A.V. Moorman, Sex ratios and the risks of haematological malignancies, Br. J. Haematol. 118 (2002) 1071-1077.
24. M.B. Cook, S.M. Dawsey, N.D. Freedman, P.D. Inskip, S.M. Wichner, S.M. Quraishi, S.S. Devesa, K.A. McGlynn, Sex disparities in cancer incidence by period and age, Cancer Epidemiol. Biomarkers Prev. 18 (2009) 1174-1182.
25. G. Edgren, L. Liang, H.O. Adami, E.T. Chang, Enigmatic sex disparities in cancer incidence, Eur. J. Epidemiol. 27 (2012) 187-196.
26. O.B. Eden, G. Harrison, S. Richards, J.S. Lilleyman, C.C. Bailey, J.M. Chessells, I.M. Hann, F.G. Hill, B.E. Gibson, Long-term follow-up of the United Kingdom Medical Research Council protocols for childhood acute lymphoblastic leukaemia, 1980-1997. Medical Research Council Childhood Leukaemia Working Party, Leukemia 14 (2000) 2307-2320.
27. S.R. Devarahally, R.K. Severson, P. Chuba, R. Thomas, K. Bhambhani, M.R. Hamre, Second malignant neoplasms after primary central nervous system malignancies of childhood and adolescence, Pediatr. Hematol. Oncol. 20 (2003) 617-625.
28. R. Molife, P. Lorigan, S. MacNeil, Gender and survival in malignant tumours, Cancer Treat. Rev. 27 (2001) 201-209.
29. R. Siegel, D. Naishadham, A. Jemal, Cancer statistics, 2012, CA Cancer J. Clin. 62 (2012) (2012) 10-29.
30. M.T. Dorak, E. Karpuzoglu, Gender differences in cancer susceptibility: an inadequately addressed issue, Front. Genet. 3 (2012) 268.
31. L.J. Zhang, Y. Xiong, N. Nilubol, M. He, S. Bommareddi, X. Zhu, L. Jia, Z. Xiao, J.W. Park, X. Xu, D.T. Patel, M.C. Willingham, S.Y. Cheng, E. Kebebew, Testosterone regulates thyroid cancer progression by modifying tumor suppressor-genes and tumor immunity, Carcinogenesis (2015).
32. J.M. Amos-Landgraf, J. Heijmans, M.C. Wielenga, E. Dunkin, K.J. Krentz, L. Clipson, A.G. Ederveen, P.G. Groothuis, S. Mosselman, V. Muncan, D.W. Hommes, A. Shedlovsky, W.F. Dove, G.R. van den Brink, Sex disparity in colonic adenomagenesis involves promotion by male hormones, not protection by female hormones, Proc. Natl. Acad. Sci. U.S.A. 111 (2014) 16514-16519.
33. J.B. Aragon-Ching, The evolution of prostate cancer therapy: targeting the androgen receptor, Front. Oncol. 4 (2014) 295.
34. H.I. Scher, G. Buchanan, W. Gerald, L.M. Butler, W.D. Tilley, Targeting the androgen receptor: improving outcomes for castration-resistant prostate cancer, Endocr. Relat. Cancer 11 (2004) 459-476.
35. C.J. Ryan, M.R. Smith, J.S. de Bono, A. Molina, C.J. Logothetis, S.P. de, K. Fizazi, P. Mainwaring, J.M. Piulats, S. Ng, J. Carles, P.F. Mulders, E. Basch, E.J. Small, F. Saad, D. Schrijvers, P.H. Van, S.D. Mukherjee, H. Suttmann, W.R. Gerritsen, T.W. Flaig, D.J. George, E.Y. Yu, E. Efstathiou, A. Pantuck, E. Winquist, C.S. Higano, M.E. Taplin, Y. Park, T. Kheoh, T. Griffin, H.I. Scher, D.E. Rathkopf, Abiraterone in metastatic prostate cancer without previous chemotherapy, N. Engl. J. Med. 368 (2013) 138-148.
36. P.J. Hendriksen, N.F. Dits, K. Kokame, A. Veldhoven, W.M. van Weerden, C.H. Bangma, J. Trapman, G. Jenster, Evolution of the androgen receptor pathway during progression of prostate cancer, Cancer Res. 66 (2006) 5012-5020.
37. J.I. Youn, D.I. Gabrilovich, The biology of myeloid-derived suppressor cells: the blessing and the curse of morphological and functional heterogeneity, Eur. J. Immunol. 40 (2010) 2969-2975.
38. P. Jayaraman, F. Parikh, E. Lopez-Rivera, Y. Hailemichael, A. Clark, G. Ma, D. Cannan, M. Ramacher, M. Kato, W.W. Overwijk, S.H. Chen, V.Y. Umansky, A.G. Sikora, Tumor-expressed inducible nitric oxide synthase controls induction of functional myeloid-derived suppressor cells through modulation of vascular endothelial growth factor release, J. Immunol. 188 (2012) 5365-5376.
39. R.S. Tacke, H.C. Lee, C. Goh, J. Courtney, S.J. Polyak, H.R. Rosen, Y.S. Hahn, Myeloid suppressor cells induced by hepatitis C virus suppress T-cell responses through the production of reactive oxygen species, Hepatology 55 (2012) 343-353.
40. J.E. Talmadge, D.I. Gabrilovich, History of myeloid-derived suppressor cells, Nat. Rev. Cancer 13 (2013) 739-752.
41. J.I. Youn, M. Collazo, I.N. Shalova, S.K. Biswas, D.I. Gabrilovich, Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice, J. Leukoc. Biol. 91 (2012) 167-181.
42. V. Moline-Velazquez, H. Cuervo, V. Vila-Del Sol, M.C. Ortega, D. Clemente, F. de Castro, Myeloid-derived suppressor cells limit the inflammation by promoting T lymphocyte apoptosis in the spinal cord of a murine model of multiple sclerosis, Brain Pathol. 21 (2011) 678-691.
43. B. Yin, G. Ma, C.Y. Yen, Z. Zhou, G.X. Wang, C.M. Divino, S. Casares, S.H. Chen, W.C. Yang, P.Y. Pan, Myeloid-derived suppressor cells prevent type 1 diabetes in murine models, J. Immunol. 185 (2010) 5828-5834.
44. A. Trigunaite, A. Khan, E. Der, A. Song, S. Varikuti, T.N. Jorgensen, Gr1 CD11b cells suppress B cell differentiation and lupus-like disease in lupus-prone male mice, Arthritis Rheum. 65 (2013) 2392-2402.
45. Y.S. Khaled, B.J. Ammori, E. Elkord, Increased levels of granulocytic myeloidderived suppressor cells in peripheral blood and tumour tissue of pancreatic cancer patients, J. Immunol. Res. 2014 (2014) 879-897.
46. B. Zhang, Z. Wang, L. Wu, M. Zhang, W. Li, J. Ding, J. Zhu, H. Wei, K. Zhao, Circulating and tumor-infiltrating myeloid-derived suppressor cells in patients with colorectal carcinoma, PLoS One 8 (2013) e57114.
47. K.H. Chuang, S. Altuwaijri, G. Li, J.J. Lai, C.Y. Chu, K.P. Lai, H.Y. Lin, J.W. Hsu, P. Keng, M.C. Wu, C. Chang, Neutropenia with impaired host defense against microbial infection in mice lacking androgen receptor, J. Exp. Med. 206 (2009) 1181-1199.
48. D.G. Arango, A. Descoteaux, Macrophage cytokines: involvement in immunity and infectious diseases, Front. Immunol. 5 (2014) 491.
49. M.H. Sieweke, J.E. Allen, Beyond stem cells: self-renewal of differentiated macrophages, Science 342 (2013) 1242974.
50. J.A. Rettew, Y.M. Huet-Hudson, I. Marriott, Testosterone reduces macrophage expression in the mouse of toll-like receptor 4, a trigger for inflammation and innate immunity, Biol. Reprod. 78 (2008) 432-437.
51. M.K. Angele, S. Pratschke, W.J. Hubbard, I.H. Chaudry, Gender differences in sepsis: cardiovascular and immunological aspects, Virulence 5 (2014) 12-19.
52. A. Matsuda, K. Furukawa, H. Suzuki, T. Matsutani, T. Tajiri, I.H. Chaudry, Dehydroepiandrosterone modulates toll-like receptor expression on splenic macrophages of mice after severe polymicrobial sepsis, Shock 24 (2005) 364-369.
53. M.C. Frantz, N.J. Prix, M.W. Wichmann, N.K. van den Engel, T. Hernandez- Richter, E. Faist, I.H. Chaudry, K.W. Jauch, M.K. Angele, Dehydroepiandrosterone restores depressed peripheral blood mononuclear cell function following major abdominal surgery via the estrogen receptors, Crit. Care Med. 33 (2005) 1779-1786.
54. M.P. Corcoran, M. Meydani, A.H. Lichtenstein, E.J. Schaefer, A. Dillard, S. Lamon-Fava, Sex hormone modulation of proinflammatory cytokine and Creactive protein expression in macrophages from older men and postmenopausal women, J. Endocrinol. 206 (2010) 217-224.
55. G. Chinetti-Gbaguidi, S. Colin, B. Staels, Macrophage subsets in atherosclerosis, Nat. Rev. Cardiol. (2014).
56. Y. Qiu, T. Yanase, H. Hu, T. Tanaka, Y. Nishi, M. Liu, K. Sueishi, T. Sawamura, H. Nawata, Dihydrotestosterone suppresses foam cell formation and attenuates atherosclerosis development, Endocrinology 151 (2010) 3307-3316.
57. R.M. Steinman, Z.A. Cohn, Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro, J. Exp. Med. 139 (1974) 380-397.
58. R.M. Steinman, J.C. Adams, Z.A. Cohn, Identification of a novel cell type in peripheral lymphoid organs of mice. IV. Identification and distribution in mouse spleen, J. Exp. Med. 141 (1975) 804-820.
59. M. Merad, P. Sathe, J. Helft, J. Miller, A. Mortha, The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting, Annu. Rev. Immunol. 31 (2013) 563-604.
60. J. Banchereau, R.M. Steinman, Dendritic cells and the control of immunity, Nature 392 (1998) 245-252.
61. R. Bonasio, M.L. Scimone, P. Schaerli, N. Grabie, A.H. Lichtman, U.H. Von Andrian, Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus, Nat. Immunol. 7 (2006) 1092-1100.
62. C. Vitali, F. Mingozzi, A. Broggi, S. Barresi, F. Zolezzi, J. Bayry, G. Raimondi, I. Zanoni, F. Granucci, Migratory, and not lymphoid-resident, dendritic cells maintain peripheral self-tolerance and prevent autoimmunity via induction of iTreg cells, Blood 120 (2012) 1237-1245.
63. C.M. Sun, J.A. Hall, R.B. Blank, N. Bouladoux, M. Oukka, J.R. Mora, Y. Belkaid, Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid, J. Exp. Med. 204 (2007) 1775-1785.
64. J.L. Coombes, K.R. Siddiqui, C.V. Arancibia-Carcamo, J. Hall, C.M. Sun, Y. Belkaid, F. Powrie, A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic aciddependent mechanism, J. Exp. Med. 204 (2007) 1757-1764.
65. M. Guilliams, K. Crozat, S. Henri, S. Tamoutounour, P. Grenot, E. Devilard, B. de Bovis, L. Alexopoulou, M. Dalod, B. Malissen, Skin-draining lymph nodes contain dermis-derived CD103(-) dendritic cells that constitutively produce retinoic acid and induce Foxp3(+) regulatory T cells, Blood 115 (2010) 1958-1968.
66. M. Bolla, D. Gonzalez, P. Warde, J.B. Dubois, R.O. Mirimanoff, G. Storme, J. Bernier, A. Kuten, C. Sternberg, T. Gil, L. Collette, M. Pierart, Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin, N. Engl. J. Med. 337 (1997) 295-300.
67. D.L. Jacobson, S.J. Gange, N.R. Rose, N.M. Graham, Epidemiology and estimated population burden of selected autoimmune diseases in the United States, Clin. Immunol. Immunopathol. 84 (1997) 223-243.
68. M.A. French, P. Hughes, Systemic lupus erythematosus and Klinefelter's syndrome, Ann. Rheum. Dis. 42 (1983) 471-473.
69. J.J. Corrales, M. Almeida, M. Cordero, L. Martin-Martin, C. Mendez, J.M. Miralles, A. Orfao, Enhanced immunological response by dendritic cells in male hypogonadism, Eur. J. Clin. Invest. 42 (2012) 1205-1212.
70. J.J. Corrales, M. Almeida, J.M. Miralles, A. Orfao, Persistence of androgenic effects on the production of proinflammatory cytokines by circulating antigen-presenting cells after withdrawal of testosterone treatment in aging type 2 diabetic men with partial androgen deficiency, Fertil. Steril. 92 (2009) 311-319.
71. U. O'Doherty, M. Peng, S. Gezelter, W.J. Swiggard, M. Betjes, N. Bhardwaj, R.M. Steinman, Human blood contains two subsets of dendritic cells, one immunologically mature and the other immature, Immunology 82 (1994) 487-493.
72. F.P. Siegal, N. Kadowaki, M. Shodell, P.A. Fitzgerald-Bocarsly, K. Shah, S. Ho, S. Antonenko, Y.J. Liu, The nature of the principal type 1 interferon-producing cells in human blood, Science 284 (1999) 1835-1837.
73. M. Cella, D. Jarrossay, F. Facchetti, O. Alebardi, H. Nakajima, A. Lanzavecchia, M. Colonna, Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon, Nat. Med. 5 (1999) 919-923.
74. S. Laffont, N. Rouquie, P. Azar, C. Seillet, J. Plumas, C. Aspord, J.C. Guery, Xchromosome complement and estrogen receptor signaling independently contribute to the enhanced TLR7-mediated IFN-alpha production of plasmacytoid dendritic cells from women, J. Immunol. 193 (2014) 5444-5452.
75. A. Meier, J.J. Chang, E.S. Chan, R.B. Pollard, H.K. Sidhu, S. Kulkarni, T.F. Wen, R.J. Lindsay, L. Orellana, D. Mildvan, S. Bazner, H. Streeck, G. Alter, J.D. Lifson, M. Carrington, R.J. Bosch, G.K. Robbins, M. Altfeld, Sex differences in the Tolllike receptor-mediated response of plasmacytoid dendritic cells to HIV-1, Nat. Med. 15 (2009) 955-959.
76. J. Henderson, On the relationship of the thymus to the sexual organs: I. The influence of castration on the thymus, J. Physiol. 31 (1904) 222-229.
77. J.S. Sutherland, G.L. Goldberg, M.V. Hammett, A.P. Uldrich, S.P. Berzins, T.S. Heng, B.R. Blazar, J.L. Millar, M.A. Malin, A.P. Chidgey, R.L. Boyd, Activation of thymic regeneration in mice and humans following androgen blockade, J. Immunol. 175 (2005) 2741-2753.
78. N.J. Olsen, G. Olson, S.M. Viselli, X. Gu, W.J. Kovacs, Androgen receptors in thymic epithelium modulate thymus size and thymocyte development, Endocrinology 142 (2001) 1278-1283.
79. T.S. Heng, G.L. Goldberg, D.H. Gray, J.S. Sutherland, A.P. Chidgey, R.L. Boyd, Effects of castration on thymocyte development in two different models of thymic involution, J. Immunol. 175 (2005) 2982-2993.
80. A.C. Roden, M.T. Moser, S.D. Tri, M. Mercader, S.M. Kuntz, H. Dong, A.A. Hurwitz, D.J. McKean, E. Celis, B.C. Leibovich, J.P. Allison, E.D. Kwon, Augmentation of T cell levels and responses induced by androgen deprivation, J. Immunol. 173 (2004) 6098-6108.
81. I. Pilipovic, K. Radojevic, D. Kosec, M.P. Nanut, Z. Stojic-Vukanic, N. Arsenovic- Ranin, G. Leposavic, Gonadal hormone dependent developmental plasticity of catecholamine:beta2-adrenoceptor signaling complex in male rat thymus: putative implications for thymopoiesis, J. Neuroimmunol. 265 (2013) 20-35.
82. T.M. Ellis, M.T. Moser, P.T. Le, R.C. Flanigan, E.D. Kwon, Alterations in peripheral B cells and B cell progenitors following androgen ablation in mice, Int. Immunol. 13 (2001) 553-558.
83. J.A. Dudakov, G.L. Goldberg, J.J. Reiseger, K. Vlahos, A.P. Chidgey, R.L. Boyd, Sex steroid ablation enhances hematopoietic recovery following cytotoxic antineoplastic therapy in aged mice, J. Immunol. 183 (2009) 7084-7094.
84. A.L. Barnard, A.P. Chidgey, C.C. Bernard, R.L. Boyd, Androgen depletion increases the efficacy of bone marrow transplantation in ameliorating experimental autoimmune encephalomyelitis, Blood 113 (2009) 204-213.
85. G.L. Goldberg, J.S. Sutherland, M.V. Hammet, M.K. Milton, T.S. Heng, A.P. Chidgey, R.L. Boyd, Sex steroid ablation enhances lymphoid recovery following autologous hematopoietic stem cell transplantation, Transplantation 80 (2005) 1604-1613.
86. N.J. Olsen, S.M. Viselli, J. Fan, W.J. Kovacs, Androgens accelerate thymocyte apoptosis, Endocrinology 139 (1998) 748-752.
87. N.J. Olsen, W.J. Kovacs, Evidence that androgens modulate human thymic T cell output, J. Investig. Med. 59 (2011) 32-35.
88. W.J. Kovacs, N.J. Olsen, Androgen receptors in human thymocytes, J. Immunol. 139 (1987) 490-493.
89. S.M. Liva, R.R. Voskuhl, Testosterone acts directly on CD4+ T lymphocytes to increase IL-10 production, J. Immunol. 167 (2001) 2060-2067.
90. B.F. Bebo Jr., J.C. Schuster, A.A. Vandenbark, H. Offner, Androgens alter the cytokine profile and reduce encephalitogenicity of myelin-reactive T cells, J. Immunol. 162 (1999) 35-40.
91. N. Kumar, L.X. Shan, M.P. Hardy, C.W. Bardin, K. Sundaram, Mechanism of androgen-induced thymolysis in rats, Endocrinology 136 (1995) 4887-4893.
92. N.J. Olsen, W.J. Kovacs, Effects of androgens on T and B lymphocyte development, Immunol. Res. 23 (2001) 281-288.
93. R.L. Mosley, M.M. Koker, R.A. Miller, Idiosyncratic alterations of TCR size distributions affecting both CD4 and CD8 T cell subsets in aging mice, Cell. Immunol. 189 (1998) 10-18.
94. J. LeMaoult, I. Messaoudi, J.S. Manavalan, H. Potvin, D. Nikolich-Zugich, R. Dyall, P. Szabo, M.E. Weksler, J. Nikolich-Zugich, Age-related dysregulation in CD8 T cell homeostasis: kinetics of a diversity loss, J. Immunol. 165 (2000) 2367-2373.
95. L. Haynes, A.C. Maue, Effects of aging on T cell function, Curr. Opin. Immunol. 21 (2009) 414-417.
96. T. Bruland, H.Y. Dai, L.A. Lavik, L.I. Kristiansen, A. Dalen, Gender-related differences in susceptibility, early virus dissemination and immunosuppression in mice infected with Friend murine leukaemia virus variant FIS-2, J. Gen. Virol. 82 (2001) 1821-1827.
97. G. Caligiuri, A. Nicoletti, X. Zhou, I. Tornberg, G.K. Hansson, Effects of sex and age on atherosclerosis and autoimmunity in apoE-deficient mice, Atherosclerosis 145 (1999) 301-308.
98. J.G. Markle, D.N. Frank, S. Mortin-Toth, C.E. Robertson, L.M. Feazel, U. Rolle- Kampczyk, M. von Bergen, K.D. McCoy, A.J. Macpherson, J.S. Danska, Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity, Science 339 (2013) 1084-1088.
99. M.G. Torcia, L. Nencioni, A.M. Clemente, L. Civitelli, I. Celestino, D. Limongi, G. Fadigati, E. Perissi, F. Cozzolino, E. Garaci, A.T. Palamara, Sex differences in the response to viral infections: TLR8 and TLR9 ligand stimulation induce higher IL10 production in males, PLoS One 7 (2012) e39853.
100. R.J. Engler, M.R. Nelson, M.M. Klote, M.J. VanRaden, C.Y. Huang, N.J. Cox, A. Klimov, W.A. Keitel, K.L. Nichol, W.W. Carr, J.J. Treanor, Half- vs full-dose trivalent inactivated influenza vaccine (2004-2005): age, dose, and sex effects on immune responses, Arch. Intern. Med. 168 (2008) 2405-2414.
101. D. Furman, B.P. Hejblum, N. Simon, V. Jojic, C.L. Dekker, R. Thiebaut, R.J. Tibshirani, M.M. Davis, Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination, Proc. Natl. Acad. Sci. U.S.A. 111 (2014) 869-874.
102. S.L. Klein, A. Jedlicka, A. Pekosz, The Xs and Y of immune responses to viral vaccines, Lancet Infect. Dis. 10 (2010) 338-349.
103. F.P. Heinzel, A.M. Hujer, F.N. Ahmed, R.M. Rerko, In vivo production and function of IL-12 p40 homodimers, J. Immunol. 158 (1997) 4381-4388.
104. R. Lai, M. Jeyanathan, C.R. Shaler, D. Damjanovic, A. Khera, C. Horvath, A.A. Ashkar, Z. Xing, Restoration of innate immune activation accelerates Th1-cell priming and protection following pulmonary mycobacterial infection, Eur. J. Immunol. 44 (2014) 1375-1386.
105. P. Scott, IFN-gamma modulates the early development of Th1 and Th2 responses in a murine model of cutaneous leishmaniasis, J. Immunol. 147 (1991) 3149-3155.
106. T. Sareneva, I. Julkunen, S. Matikainen, IFN-alpha and IL-12 induce IL-18 receptor gene expression in human NK and T cells, J. Immunol. 165 (2000) 1933-1938.
107. Y.Y. Wan, R.A. Flavell, How diverse - CD4 effector T cells and their functions, J. Mol. Cell Biol. 1 (2009) 20-36.
108. T. Zhang, K. Kawakami, M.H. Qureshi, H. Okamura, M. Kurimoto, A. Saito, Interleukin-12 (IL-12) and IL-18 synergistically induce the fungicidal activity of murine peritoneal exudate cells against Cryptococcus neoformans through production of gamma interferon by natural killer cells, Infect. Immun. 65 (1997) 3594-3599.
109. K. Assani, M.F. Tazi, A.O. Amer, B.T. Kopp, IFN-gamma stimulates autophagymediated clearance of Burkholderia cenocepacia in human cystic fibrosis macrophages, PLoS One 9 (2014) e96681.
110. I.K. Choi, Y. Li, E. Oh, J. Kim, C.O. Yun, Oncolytic adenovirus expressing IL-23 and p35 elicits IFN-gamma- and TNF-alpha-co-producing T cell-mediated antitumor immunity, PLoS One 8 (2013) e67512.
111. S.A. Gerber, A.L. Sedlacek, K.R. Cron, S.P. Murphy, J.G. Frelinger, E.M. Lord, IFNgamma mediates the antitumor effects of radiation therapy in a murine colon tumor, Am. J. Pathol. 182 (2013) 2345-2354.
112. M.J. Micallef, T. Ohtsuki, K. Kohno, F. Tanabe, S. Ushio, M. Namba, T. Tanimoto, K. Torigoe, M. Fujii, M. Ikeda, S. Fukuda, Interferon-gammainducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin-12 for interferon-gamma production, Eur. J. Immunol. 26 (1996) 1647-1651.
113. N.J. Davidson, M.W. Leach, M.M. Fort, L. Thompson-Snipes, R. Kuhn, W. Muller, D.J. Berg, D.M. Rennick, T helper cell 1-type CD4+ T cells, but not B cells, mediate colitis in interleukin 10-deficient mice, J. Exp. Med. 184 (1996) 241-251.
114. H.Z. Hu, G.L. Li, Y.K. Lim, S.H. Chan, E.H. Yap, Kinetics of interferon-gamma secretion and its regulatory factors in the early phase of acute graft-versushost disease, Immunology 98 (1999) 379-385.
115. B.P. Leung, I.B. McInnes, E. Esfandiari, X.Q. Wei, F.Y. Liew, Combined effects of IL-12 and IL-18 on the induction of collagen-induced arthritis, J. Immunol. 164 (2000) 6495-6502.
116. B. Wang, I. Andre, A. Gonzalez, J.D. Katz, M. Aguet, C. Benoist, D. Mathis, Interferon-gamma impacts at multiple points during the progression of autoimmune diabetes, Proc. Natl. Acad. Sci. U.S.A. 94 (1997) 13844-13849.
117. X. Filella, J. Alcover, M.A. Zarco, P. Beardo, R. Molina, A.M. Ballesta, Analysis of type T1 and T2 cytokines in patients with prostate cancer, Prostate 44 (2000) 271-274.
118. M. Sato, S. Goto, R. Kaneko, M. Ito, S. Sato, S. Takeuchi, Impaired production of Th1 cytokines and increased frequency of Th2 subsets in PBMC from advanced cancer patients, Anticancer Res. 18 (1998) 3951-3955.
119. C.S. Constantinescu, N. Farooqi, K. O'Brien, B. Gran, Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS), Br. J. Pharmacol. 164 (2011) 1079-1106.
120. S.J. Khoury, L. Gallon, W. Chen, K. Betres, M.E. Russell, W.W. Hancock, C.B. Carpenter, M.H. Sayegh, H.L. Weiner, Mechanisms of acquired thymic tolerance in experimental autoimmune encephalomyelitis: thymic dendritic-enriched cells induce specific peripheral T cell unresponsiveness in vivo, J. Exp. Med. 182 (1995) 357-366.
121. M. Dalal, S. Kim, R.R. Voskuhl, Testosterone therapy ameliorates experimental autoimmune encephalomyelitis and induces a T helper 2 bias in the autoantigen-specific T lymphocyte response, J. Immunol. 159 (1997) 3-6.
122. H.T. Kissick, M.G. Sanda, L.K. Dunn, K.L. Pellegrini, S.T. On, J.K. Noel, M.S. Arredouani, Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation, Proc. Natl. Acad. Sci. U.S.A. 111 (2014) 9887-9892.
123. M.P. Myers, J.N. Andersen, A. Cheng, M.L. Tremblay, C.M. Horvath, J.P. Parisien, A. Salmeen, D. Barford, N.K. Tonks, TYK2 and JAK2 are substrates of protein-tyrosine phosphatase 1B, J. Biol. Chem. 276 (2001) 47771-47774.
124. G. Fan, G. Lin, R. Lucito, N.K. Tonks, Protein-tyrosine phosphatase 1B antagonized signaling by insulin-like growth factor-1 receptor and kinase BRK/PTK6 in ovarian cancer cells, J. Biol. Chem. 288 (2013) 24923-24934.
125. M.R. Hepworth, M.J. Hardman, R.K. Grencis, The role of sex hormones in the development of Th2 immunity in a gender-biased model of Trichuris muris infection, Eur. J. Immunol. 40 (2010) 406-416.
126. K. Itoh, S. Hirohata, The role of IL-10 in human B cell activation, proliferation, and differentiation, J. Immunol. 154 (1995) 4341-4350.
127. F. Rousset, E. Garcia, T. Defrance, C. Peronne, N. Vezzio, D.H. Hsu, R. Kastelein, K.W. Moore, J. Banchereau, Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes, Proc. Natl. Acad. Sci. U.S.A. 89 (1992) 1890-1893.
128. T. De Smedt, M.M. Van, G. De Becker, J. Urbain, O. Leo, M. Moser, Effect of interleukin-10 on dendritic cell maturation and function, Eur. J. Immunol. 27 (1997) 1229-1235.
129. C. Haase, T.N. Jorgensen, B.K. Michelsen, Both exogenous and endogenous IL- 10 affects maturation of bone-marrow derived dendritic cells in vitro and strongly influences T cell priming in vivo, Immunology 107 (2002) 489-499.
130. E.J. Pearce, M. Kane, J. Sun, J. Taylor, A.S. McKee, L. Cervi, Th2 response polarization during infection with the helminth parasite Schistosoma mansoni, Immunol. Rev. 201 (2004) 117-126.
131. M. Fijak, E. Schneider, J. Klug, S. Bhushan, H. Hackstein, G. Schuler, M. Wygrecka, J. Gromoll, A. Meinhardt, Testosterone replacement effectively inhibits the development of experimental autoimmune orchitis in rats: evidence for a direct role of testosterone on regulatory T cell expansion, J. Immunol. 186 (2011) 5162-5172.
132. S. Tang, M.L. Moore, J.M. Grayson, P. Dubey, Increased CD8+ T-cell function following castration and immunization is countered by parallel expansion of regulatory T cells, Cancer Res. 72 (2012) 1975-1985.
133. C. Nicoletti, Antibody response in aged C57BL/6 mice: T helper cells are responsible for the decline of the primary antibody response to a bacterial antigen in aging, Immunobiology 190 (1994) 127-137.
134. M. Frey-Wettstein, C.G. Craddock, Testosterone-induced depletion of thymus and marrow lymphocytes as related to lymphopoiesis and hematopoiesis, Blood 35 (1970) 257-271.
135. G. Smithson, W.G. Beamer, K.L. Shultz, S.W. Christianson, L.D. Shultz, P.W. Kincade, Increased B lymphopoiesis in genetically sex steroid-deficient hypogonadal (hpg) mice, J. Exp. Med. 180 (1994) 717-720.
136. S.M. Viselli, K.R. Reese, J. Fan, W.J. Kovacs, N.J. Olsen, Androgens alter B cell development in normal male mice, Cell. Immunol. 182 (1997) 99-104.
137. G. Smithson, J.F. Couse, D.B. Lubahn, K.S. Korach, P.W. Kincade, The role of estrogen receptors and androgen receptors in sex steroid regulation of B lymphopoiesis, J. Immunol. 161 (1998) 27-34.
138. K.H. Grabstein, T.J. Waldschmidt, F.D. Finkelman, B.W. Hess, A.R. Alpert, N.E. Boiani, A.E. Namen, P.J. Morrissey, Inhibition of murine B and T lymphopoiesis in vivo by an anti-interleukin 7 monoclonal antibody, J. Exp. Med. 178 (1993) 257-264.
139. N.J. Olsen, X. Gu, W.J. Kovacs, Bone marrow stromal cells mediate androgenic suppression of B lymphocyte development, J. Clin. Invest. 108 (2001) 1697-1704.
140. J. Tang, B.L. Nuccie, I. Ritterman, J.L. Liesveld, C.N. Abboud, D.H. Ryan, TGFbeta down-regulates stromal IL-7 secretion and inhibits proliferation of human B cell precursors, J. Immunol. 159 (1997) 117-125.
141. S. Altuwaijri, K.H. Chuang, K.P. Lai, J.J. Lai, H.Y. Lin, F.M. Young, A. Bottaro, M.Y. Tsai, W.P. Zeng, H.C. Chang, S. Yeh, C. Chang, Susceptibility to autoimmunity and B cell resistance to apoptosis in mice lacking androgen receptor in B cells, Mol. Endocrinol. 23 (2009) 444-453.