The immune system is a natural target for estrogen action: Opposing effects of estrogen in two prototypical autoimmune diseases

Frontiers in Immunology

Volumn 6, Issue JAN, 2016, Pages

  Khan, Deena ^a   Ansar Ahmed, S ^a  

^a VIRGINIA MARYLAND REGIONAL COLLEGE OF VETERINARY MEDICINE   (United States)

Author keywords

Autoimmune; Estrogen; Immune cell; MS; Signaling; SLE

Indexed keywords

ESTROGEN RECEPTOR; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA;

ACETYLATION; ADAPTIVE IMMUNITY; AUTOIMMUNE DISEASE; B LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DIFFERENTIATION; CYTOKINE PRODUCTION; GENE EXPRESSION; HUMAN; IMMUNE SYSTEM; INNATE IMMUNITY; MULTIPLE SCLEROSIS; MYRISTYLATION; NONHUMAN; PALMITOYLATION; PHAGOCYTOSIS; SHORT SURVEY; SIGNAL TRANSDUCTION; SUMOYLATION; SYSTEMIC LUPUS ERYTHEMATOSUS; UBIQUITINATION;

EID: 84958178503     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2015.00635     Document Type: Short Survey

References (112)

1. Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med (1994) 331(16):1056-61. doi:10.1056/NEJM199410203311604
2. Carani C, Qin K, Simoni M, Faustini-Fustini M, Serpente S, Boyd J, et al. Effect of testosterone and estradiol in a man with aromatase deficiency. N Engl J Med (1997) 337(2):91-5. doi:10.1056/NEJM199707103370204
3. Gustafsson JA. What pharmacologists can learn from recent advances in estrogen signalling. Trends Pharmacol Sci (2003) 24(9):479-85. doi:10.1016/S0165-6147(03)00229-3
4. Ansar Ahmed S, Karpuzoglu E, Khan D. Effect of sex steroids on innate and adaptive immunity. In: Klein SL, Roberts CW, editors. Sex Hormones and Immunity to Infection. London: Springer (2010). p. 19-51.
5. Khan D, Cowan C, Ansar Ahmed S. Estrogen and signaling in the cells of immune system. Adv Neuroimm Biol (2012) 3(1):73-93. doi:10.3233/NIB-2012-012039
6. Kovats S. Estrogen receptors regulate an inflammatory pathway of dendritic cell differentiation: mechanisms and implications for immunity. Horm Behav (2012) 62(3):254-62. doi:10.1016/j.yhbeh.2012.04.011
7. Kovats S. Estrogen receptors regulate innate immune cells and signaling pathways. Cell Immunol (2015) 294(2):63-9. doi:10.1016/j.cellimm.2015.01.018
8. Hsu JT, Kan WH, Hsieh CH, Choudhry MA, Schwacha MG, Bland KI, et al. Mechanism of estrogen-mediated attenuation of hepatic injury following trauma-hemorrhage: Akt-dependent HO-1 up-regulation. J Leukoc Biol (2007) 82(4):1019-26. doi:10.1189/jlb.0607355
9. Yu HP, Hsieh YC, Suzuki T, Choudhry MA, Schwacha MG, Bland KI, et al. Mechanism of the nongenomic effects of estrogen on intestinal myeloperoxidase activity following trauma-hemorrhage: up-regulation of the PI-3K/Akt pathway. J Leukoc Biol (2007) 82(3):774-80. doi:10.1189/jlb.0307182
10. Cuzzocrea S, Genovese T, Mazzon E, Esposito E, Di Paola R, Muia C, et al. Effect of 17beta-estradiol on signal transduction pathways and secondary damage in experimental spinal cord trauma. Shock (2008) 29(3):362-71. doi:10.1097/SHK.0b013e31814545dc
11. Cowan C, Dai R, Heid B, Ansar Ahmed S. Phenotypic and functional characterization of neutrophils from lupus-prone mice. American Association of Immunologists Annual Meeting, Immunology 2014. Pittsburg, PA (2014).
12. Cutolo M, Sulli A, Capellino S, Villaggio B, Montagna P, Seriolo B, et al. Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity. Lupus (2004) 13(9):635-8. doi:10.1191/0961203304lu1094oa
13. Karpuzoglu E, Ansar Ahmed S. Estrogen regulation of nitric oxide and inducible nitric oxide synthase (iNOS) in immune cells: implications for immunity, autoimmune diseases, and apoptosis. Nitric Oxide (2006) 15(3):177-86. doi:10.1016/j.niox.2006.03.009
14. Dai R, Phillips RA, Zhang Y, Khan D, Crasta O, Ansar Ahmed S. Suppression of LPS-induced Interferon-gamma and nitric oxide in splenic lymphocytes by select estrogen-regulated microRNAs: a novel mechanism of immune modulation. Blood (2008) 112(12):4591-7. doi:10.1182/blood-2007-10-116376
15. Hsieh CH, Nickel EA, Chen J, Schwacha MG, Choudhry MA, Bland KI, et al. Mechanism of the salutary effects of estrogen on kupffer cell phagocytic capacity following trauma-hemorrhage: pivotal role of Akt activation. J Immunol (2009) 182(7):4406-14. doi:10.4049/jimmunol.0803423
16. Karpuzoglu E, Phillips RA, Dai R, Graniello C, Gogal RM Jr, Ansar Ahmed S. Signal transducer and activation of transcription (STAT) 4beta, a shorter isoform of interleukin-12-induced STAT4, is preferentially activated by estrogen. Endocrinology (2009) 150(3):1310-20. doi:10.1210/en.2008-0832
17. Liu HY, Buenafe AC, Matejuk A, Ito A, Zamora A, Dwyer J, et al. Estrogen inhibition of EAE involves effects on dendritic cell function. J Neurosci Res (2002) 70(2):238-48. doi:10.1002/jnr.10454
18. Bachy V, Williams DJ, Ibrahim MA. Altered dendritic cell function in normal pregnancy. J Reprod Immunol (2008) 78(1):11-21. doi:10.1016/j.jri.2007.09.004
19. Cunningham MA, Wirth JR, Naga O, Eudaly J, Gilkeson GS. Estrogen receptor alpha binding to ERE is required for full Tlr7-and Tlr9-induced inflammation. SOJ Immunol (2014) 2(1):7. doi:10.15226/soji.2014.00107
20. Laffont S, Rouquie N, Azar P, Seillet C, Plumas J, Aspord C, et al. X-Chromosome complement and estrogen receptor signaling independently contribute to the enhanced TLR7-mediated IFN-alpha production of plasmacytoid dendritic cells from women. J Immunol (2014) 193(11):5444-52. doi:10.4049/jimmunol.1303400
21. Stojic-Vukanic Z, Nacka-Aleksic M, Bufan B, Pilipovic I, Arsenovic-Ranin N, Djikic J, et al. 17beta-Estradiol influences in vitro response of aged rat splenic conventional dendritic cells to TLR4 and TLR7/8 agonists in an agonist specific manner. Int Immunopharmacol (2015) 24(1):24-35. doi:10.1016/j.intimp.2014.11.008
22. Papenfuss TL, Powell ND, McClain MA, Bedarf A, Singh A, Gienapp IE, et al. Estriol generates tolerogenic dendritic cells in vivo that protect against autoimmunity. J Immunol (2011) 186(6):3346-55. doi:10.4049/jimmunol.1001322
23. Grasso G, Muscettola M. The influence of beta-estradiol and progesterone on interferon gamma production in vitro. Int J Neurosci (1990) 51(3-4):315-7. doi:10.3109/00207459008999730
24. Fox HS, Bond BL, Parslow TG. Estrogen regulates the IFN-gamma promoter. J Immunol (1991) 146(12):4362-7.
25. Karpuzoglu-Sahin E, Hissong BD, Ansar Ahmed S. Interferon-gamma levels are upregulated by 17-beta-estradiol and diethylstilbestrol. J Reprod Immunol (2001) 52(1-2):113-27. doi:10.1016/S0165-0378(01)00117-6
26. Lambert KC, Curran EM, Judy BM, Milligan GN, Lubahn DB, Estes DM. Estrogen receptor alpha (ERalpha) deficiency in macrophages results in increased stimulation of CD4+ T cells while 17beta-estradiol acts through ERalpha to increase IL-4 and GATA-3 expression in CD4+ T cells independent of antigen presentation. J Immunol (2005) 175(9):5716-23. doi:10.4049/jimmunol.175.9.5716
27. Polanczyk MJ, Carson BD, Subramanian S, Afentoulis M, Vandenbark AA, Ziegler SF, et al. Cutting edge: estrogen drives expansion of the CD4+CD25+ regulatory T cell compartment. J Immunol (2004) 173(4):2227-30. doi:10.4049/jimmunol.173.4.2227
28. Polanczyk MJ, Hopke C, Huan J, Vandenbark AA, Offner H. Enhanced FoxP3 expression and Treg cell function in pregnant and estrogen-treated mice. J Neuroimmunol (2005) 170(1-2):85-92. doi:10.1016/j.jneuroim.2005.08.023
29. Polanczyk MJ, Hopke C, Vandenbark AA, Offner H. Treg suppressive activity involves estrogen-dependent expression of programmed death-1 (PD-1). Int Immunol (2007) 19(3):337-43. doi:10.1093/intimm/dxl151
30. Tai P, Wang J, Jin H, Song X, Yan J, Kang Y, et al. Induction of regulatory T cells by physiological level estrogen. J Cell Physiol (2008) 214(2):456-64. doi:10.1002/jcp.21221
31. Grimaldi CM, Cleary J, Dagtas AS, Moussai D, Diamond B. Estrogen alters thresholds for B cell apoptosis and activation. J Clin Invest (2002) 109(12):1625-33. doi:10.1172/JCI0214873
32. Lelu K, Laffont S, Delpy L, Paulet PE, Perinat T, Tschanz SA, et al. Estrogen receptor alpha signaling in T lymphocytes is required for estradiol-mediated inhibition of Th1 and Th17 cell differentiation and protection against experimental autoimmune encephalomyelitis. J Immunol (2011) 187(5):2386-93. doi:10.4049/jimmunol.1101578
33. Priyanka HP, Krishnan HC, Singh RV, Hima L, Thyagarajan S. Estrogen modulates in vitro T cell responses in a concentration-and receptor-dependent manner: effects on intracellular molecular targets and antioxidant enzymes. Mol Immunol (2013) 56(4):328-39. doi:10.1016/j.molimm.2013.05.226
34. Robinson DP, Hall OJ, Nilles TL, Bream JH, Klein SL. 17beta-estradiol protects females against influenza by recruiting neutrophils and increasing virus-specific CD8 T cell responses in the lungs. J Virol (2014) 88(9):4711-20. doi:10.1128/JVI.03609-13
35. Karpuzoglu-Sahin E, Zhi-Jun Y, Lengi A, Sriranganathan N, Ansar Ahmed S. Effects of long-term estrogen treatment on IFN-gamma, IL-2 and IL-4 gene expression and protein synthesis in spleen and thymus of normal C57BL/6 mice. Cytokine (2001) 14(4):208-17. doi:10.1006/cyto.2001.0876
36. Karpuzoglu E, Phillips RA, Gogal RM Jr, Ansar Ahmed S. IFN-gamma-inducing transcription factor, T-bet is upregulated by estrogen in murine splenocytes: role of IL-27 but not IL-12. Mol Immunol (2007) 44(7):1819-25. doi:10.1016/j.molimm.2006.08.005
37. Maret A, Coudert JD, Garidou L, Foucras G, Gourdy P, Krust A, et al. Estradiol enhances primary antigen-specific CD4 T cell responses and Th1 development in vivo. Essential role of estrogen receptor alpha expression in hematopoietic cells. Eur J Immunol (2003) 33(2):512-21. doi:10.1002/immu.200310027
38. Matejuk A, Adlard K, Zamora A, Silverman M, Vandenbark AA, Offner H. 17 beta-estradiol inhibits cytokine, chemokine, and chemokine receptor mRNA expression in the central nervous system of female mice with experimental autoimmune encephalomyelitis. J Neurosci Res (2001) 65(6):529-42. doi:10.1002/jnr.1183
39. Sakazaki F, Ueno H, Nakamuro K. 17beta-Estradiol enhances expression of inflammatory cytokines and inducible nitric oxide synthase in mouse contact hypersensitivity. Int Immunopharmacol (2008) 8(5):654-60. doi:10.1016/j.intimp.2008.01.007
40. Verthelyi D, Klinman DM. Sex hormone levels correlate with the activity of cytokine-secreting cells in vivo. Immunology (2000) 100(3):384-90. doi:10.1046/j.1365-2567.2000.00047.x
41. Sabahi F, Rola-Plesczcynski M, O'Connell S, Frenkel LD. Qualitative and quantitative analysis of T lymphocytes during normal human pregnancy. Am J Reprod Immunol (1995) 33(5):381-93. doi:10.1111/j.1600-0897.1995.tb00907.x
42. Marzi M, Vigano A, Trabattoni D, Villa ML, Salvaggio A, Clerici E, et al. Characterization of type 1 and type 2 cytokine production profile in physiologic and pathologic human pregnancy. Clin Exp Immunol (1996) 106(1):127-33. doi:10.1046/j.1365-2249.1996.d01-809.x
43. Matalka KZ. The effect of estradiol, but not progesterone, on the production of cytokines in stimulated whole blood, is concentration-dependent. Neuro Endocrinol Lett (2003) 24(3-4):185-91.
44. Konermann A, Winter J, Novak N, Allam JP, Jager A. Verification of IL-17A and IL-17F in oral tissues and modulation of their expression pattern by steroid hormones. Cell Immunol (2013) 285(1-2):133-40. doi:10.1016/j.cellimm.2013.10.004
45. Wang Y, Cela E, Gagnon S, Sweezey NB. Estrogen aggravates inflammation in Pseudomonas aeruginosa pneumonia in cystic fibrosis mice. Respir Res (2010) 11:166. doi:10.1186/1465-9921-11-166
46. Molnar I, Bohaty I, Somogyine-Vari E. High prevalence of increased interleukin-17A serum levels in postmenopausal estrogen deficiency. Menopause (2014) 21(7):749-52. doi:10.1097/GME.0000000000000125
47. Polanczyk M, Zamora A, Subramanian S, Matejuk A, Hess DL, Blankenhorn EP, et al. The protective effect of 17beta-estradiol on experimental autoimmune encephalomyelitis is mediated through estrogen receptor-alpha. Am J Pathol (2003) 163(4):1599-605. doi:10.1016/S0002-9440(10)63516-X
48. Offner H, Polanczyk M. A potential role for estrogen in experimental autoimmune encephalomyelitis and multiple sclerosis. Ann N Y Acad Sci (2006) 1089:343-72. doi:10.1196/annals.1386.021
49. Verthelyi DI, Ansar Ahmed S. Estrogen increases the number of plasma cells and enhances their autoantibody production in nonautoimmune C57BL/6 mice. Cell Immunol (1998) 189(2):125-34. doi:10.1006/cimm.1998.1372
50. Grimaldi CM, Jeganathan V, Diamond B. Hormonal regulation of B cell development: 17 beta-estradiol impairs negative selection of high-affinity DNA-reactive B cells at more than one developmental checkpoint. J Immunol (2006) 176(5):2703-10. doi:10.4049/jimmunol.176.5.2703
51. Bernardi AI, Andersson A, Grahnemo L, Nurkkala-Karlsson M, Ohlsson C, Carlsten H, et al. Effects of lasofoxifene and bazedoxifene on B cell development and function. Immun Inflamm Dis (2014) 2(4):214-25. doi:10.1002/iid3.37
52. Hill L, Jeganathan V, Chinnasamy P, Grimaldi C, Diamond B. Differential roles of estrogen receptors alpha and beta in control of B-cell maturation and selection. Mol Med (2011) 17(3-4):211-20. doi:10.2119/molmed.2010.00172
53. Thomas C, Gustafsson JA. The different roles of ER subtypes in cancer biology and therapy. Nat Rev Cancer (2011) 11(8):597-608. doi:10.1038/nrc3093-c2
54. Krege JH, Hodgin JB, Couse JF, Enmark E, Warner M, Mahler JF, et al. Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proc Natl Acad Sci USA (1998) 95(26):15677-82. doi:10.1073/pnas.95.26.15677
55. Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, et al. Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science (1995) 270(5241):1491-4. doi:10.1126/science.270.5241.1491
56. Kawashima I, Seiki K, Sakabe K, Ihara S, Akatsuka A, Katsumata Y. Localization of estrogen receptors and estrogen receptor-mRNA in female mouse thymus. Thymus (1992) 20(2):115-21.
57. Seiki K, Sakabe K. Sex hormones and the thymus in relation to thymocyte proliferation and maturation. Arch Histol Cytol (1997) 60(1):29-38. doi:10.1679/aohc.60.29
58. Mor G, Munoz A, Redlinger R Jr, Silva I, Song J, Lim C, et al. The role of the Fas/Fas ligand system in estrogen-induced thymic alteration. Am J Reprod Immunol (2001) 46(4):298-307. doi:10.1034/j.1600-0897.2001.d01-16.x
59. Carreras E, Turner S, Paharkova-Vatchkova V, Mao A, Dascher C, Kovats S. Estradiol acts directly on bone marrow myeloid progenitors to differentially regulate GM-CSF or Flt3 ligand-mediated dendritic cell differentiation. J Immunol (2008) 180(2):727-38. doi:10.4049/jimmunol.180.2.727
60. Lambert KC, Curran EM, Judy BM, Lubahn DB, Estes DM. Estrogen receptor-alpha deficiency promotes increased TNF-alpha secretion and bacterial killing by murine macrophages in response to microbial stimuli in vitro. J Leukoc Biol (2004) 75(6):1166-72. doi:10.1189/jlb.1103589
61. Brandenberger AW, Tee MK, Lee JY, Chao V, Jaffe RB. Tissue distribution of estrogen receptors alpha (ER-alpha) and beta (ER-beta) mRNA in the midgestational human fetus. J Clin Endocrinol Metab (1997) 82(10):3509-12. doi:10.1210/jcem.82.10.4400
62. Smithson G, Couse JF, Lubahn DB, Korach KS, Kincade PW. The role of estrogen receptors and androgen receptors in sex steroid regulation of B lymphopoiesis. J Immunol (1998) 161(1):27-34.
63. Vidal O, Kindblom LG, Ohlsson C. Expression and localization of estrogen receptor-beta in murine and human bone. J Bone Miner Res (1999) 14(6):923-9. doi:10.1359/jbmr.1999.14.6.923
64. Phiel KL, Henderson RA, Adelman SJ, Elloso MM. Differential estrogen receptor gene expression in human peripheral blood mononuclear cell populations. Immunol Lett (2005) 97(1):107-13. doi:10.1016/j.imlet.2004.10.007
65. Staples JE, Gasiewicz TA, Fiore NC, Lubahn DB, Korach KS, Silverstone AE. Estrogen receptor alpha is necessary in thymic development and estradiol-induced thymic alterations. J Immunol (1999) 163(8):4168-74.
66. Erlandsson MC, Ohlsson C, Gustafsson JA, Carlsten H. Role of oestrogen receptors alpha and beta in immune organ development and in oestrogen-mediated effects on thymus. Immunology (2001) 103(1):17-25. doi:10.1046/j.1365-2567.2001.01212.x
67. Shim GJ, Kis LL, Warner M, Gustafsson JA. Autoimmune glomerulonephritis with spontaneous formation of splenic germinal centers in mice lacking the estrogen receptor alpha gene. Proc Natl Acad Sci USA (2004) 101(6):1720-4. doi:10.1073/pnas.0405099101
68. Ascenzi P, Bocedi A, Marino M. Structure-function relationship of estrogen receptor alpha and beta: impact on human health. Mol Aspects Med (2006) 27(4):299-402. doi:10.1016/j.mam.2006.07.001
69. Ansar Ahmed S, Penhale WJ, Talal N. Sex hormones, immune responses, and autoimmune diseases. Mechanisms of sex hormone action. Am J Pathol (1985) 121(3):531-51.
70. Harbo HF, Gold R, Tintore M. Sex and gender issues in multiple sclerosis. Ther Adv Neurol Disord (2013) 6(4):237-48. doi:10.1177/1756285613488434
71. Spence RD, Wisdom AJ, Cao Y, Hill HM, Mongerson CR, Stapornkul B, et al. Estrogen mediates neuroprotection and anti-inflammatory effects during EAE through ERalpha signaling on astrocytes but not through ERbeta signaling on astrocytes or neurons. J Neurosci (2013) 33(26):10924-33. doi:10.1523/JNEUROSCI.0886-13.2013
72. Khalaj AJ, Yoon J, Nakai J, Winchester Z, Moore SM, Yoo T, et al. Estrogen receptor (ER) beta expression in oligodendrocytes is required for attenuation of clinical disease by an ERbeta ligand. Proc Natl Acad Sci U S A (2013) 110(47):19125-30. doi:10.1073/pnas.1311763110
73. MacKenzie-Graham AJ, Rinek GA, Avedisian A, Morales LB, Umeda E, Boulat B, et al. Estrogen treatment prevents gray matter atrophy in experimental autoimmune encephalomyelitis. J Neurosci Res (2012) 90(7):1310-23. doi:10.1002/jnr.23019
74. Pettersson A, Ciumas C, Chirsky V, Link H, Huang YM, Xiao BG. Dendritic cells exposed to estrogen in vitro exhibit therapeutic effects in ongoing experimental allergic encephalomyelitis. J Neuroimmunol (2004) 156(1-2):58-65. doi:10.1016/j.jneuroim.2004.07.004
75. Xiao BG, Liu X, Link H. Antigen-specific T cell functions are suppressed over the estrogen-dendritic cell-indoleamine 2,3-dioxygenase axis. Steroids (2004) 69(10):653-9. doi:10.1016/j.steroids.2004.05.019
76. Matejuk A, Dwyer J, Hopke C, Vandenbark AA, Offner H. 17Beta-estradiol treatment profoundly down-regulates gene expression in spinal cord tissue in mice protected from experimental autoimmune encephalomyelitis. Arch Immunol Ther Exp (Warsz) (2003) 51(3):185-93.
77. Gatson NN, Williams JL, Powell ND, McClain MA, Hennon TR, Robbins PD, et al. Induction of pregnancy during established EAE halts progression of CNS autoimmune injury via pregnancy-specific serum factors. J Neuroimmunol (2011) 230(1-2):105-13. doi:10.1016/j.jneuroim.2010.09.010
78. Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med (1998) 339(5):285-91. doi:10.1056/NEJM199807303390501
79. Vukusic S, Hutchinson M, Hours M, Moreau T, Cortinovis-Tourniaire P, Adeleine P, et al. Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse. Brain (2004) 127(Pt 6):1353-60. doi:10.1093/brain/awh152
80. Beeson PB. Age and sex associations of 40 autoimmune diseases. Am J Med (1994) 96(5):457-62. doi:10.1016/0002-9343(94)90173-2
81. Lockshin MD. Sex ratio and rheumatic disease: excerpts from an Institute of Medicine report. Lupus (2002) 11(10):662-6. doi:10.1191/0961203302lu274oa
82. Yacoub Wasef SZ. Gender differences in systemic lupus erythematosus. Gend Med (2004) 1(1):12-7. doi:10.1016/S1550-8579(04)80006-8
83. Straub RH. The complex role of estrogens in inflammation. Endocr Rev (2007) 28(5):521-74. doi:10.1210/er.2007-0001
84. Kassi E, Moutsatsou P. Estrogen receptor signaling and its relationship to cytokines in systemic lupus erythematosus. J Biomed Biotechnol (2010) 2010:317452. doi:10.1155/2010/317452
85. Kanda N, Tamaki K. Estrogen enhances immunoglobulin production by human PBMCs. J Allergy Clin Immunol (1999) 103(2 Pt 1):282-8. doi:10.1016/S0091-6749(99)70503-8
86. Durali D, de Goer de Herve MG, Giron-Michel J, Azzarone B, Delfraissy JF, Taoufik Y. In human B cells, IL-12 triggers a cascade of molecular events similar to Th1 commitment. Blood (2003) 102(12):4084-9. doi:10.1182/blood-2003-02-0518
87. Sekigawa I, Naito T, Hira K, Mitsuishi K, Ogasawara H, Hashimoto H, et al. Possible mechanisms of gender bias in SLE: a new hypothesis involving a comparison of SLE with atopy. Lupus (2004) 13(4):217-22. doi:10.1191/0961203304lu1012ed
88. Perl A, Nagy G, Koncz A, Gergely P, Fernandez D, Doherty E, et al. Molecular mimicry and immunomodulation by the HRES-1 endogenous retrovirus in SLE. Autoimmunity (2008) 41(4):287-97. doi:10.1080/08916930802024764
89. Venkatesh J, Yoshifuji H, Kawabata D, Chinnasamy P, Stanevsky A, Grimaldi CM, et al. Antigen is required for maturation and activation of pathogenic anti-DNA antibodies and systemic inflammation. J Immunol (2011) 186(9):5304-12. doi:10.4049/jimmunol.1000224
90. Kawasaki M, Sekigawa I, Nozawa K, Kaneko H, Takasaki Y, Takamori K, et al. Changes in the gene expression of peripheral blood mononuclear cells during the menstrual cycle of females is associated with a gender bias in the incidence of systemic lupus erythematosus. Clin Exp Rheumatol (2009) 27(2):260-6.
91. Sedy JR, Gavrieli M, Potter KG, Hurchla MA, Lindsley RC, Hildner K, et al. B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator. Nat Immunol (2005) 6(1):90-8. doi:10.1038/ni1144
92. Cai G, Freeman GJ. The CD160, BTLA, LIGHT/HVEM pathway: a bidirectional switch regulating T-cell activation. Immunol Rev (2009) 229(1):244-58. doi:10.1111/j.1600-065X.2009.00783.x
93. Greenstein B, Roa R, Dhaher Y, Nunn E, Greenstein A, Khamashta M, et al. Estrogen and progesterone receptors in murine models of systemic lupus erythematosus. Int Immunopharmacol (2001) 1(6):1025-35. doi:10.1016/S1567-5769(01)00034-0
94. Inui A, Ogasawara H, Naito T, Sekigawa I, Takasaki Y, Hayashida Y, et al. Estrogen receptor expression by peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Clin Rheumatol (2007) 26(10):1675-8. doi:10.1007/s10067-007-0568-3
95. Feng F, Nyland J, Banyai M, Tatum A, Silverstone AE, Gavalchin J. The induction of the lupus phenotype by estrogen is via an estrogen receptor-alpha-dependent pathway. Clin Immunol (2010) 134(2):226-36. doi:10.1016/j.clim.2009.10.004
96. Li J, McMurray RW. Effects of estrogen receptor subtype-selective agonists on autoimmune disease in lupus-prone NZB/NZW F1 mouse model. Clin Immunol (2007) 123(2):219-26. doi:10.1016/j.clim.2007.03.471
97. Lee YJ, Shin KS, Kang SW, Lee CK, Yoo B, Cha HS, et al. Association of the oestrogen receptor alpha gene polymorphisms with disease onset in systemic lupus erythematosus. Ann Rheum Dis (2004) 63(10):1244-9. doi:10.1136/ard.2003.012583
98. Johansson M, Arlestig L, Moller B, Smedby T, Rantapaa-Dahlqvist S. Oestrogen receptor α gene polymorphisms in systemic lupus erythematosus. Ann Rheum Dis (2005) 64(11):1611-7. doi:10.1136/ard.2004.032425
99. Choubey D, Panchanathan R. Interferon-inducible Ifi200-family genes in systemic lupus erythematosus. Immunol Lett (2008) 119(1-2):32-41. doi:10.1016/j.imlet.2008.06.001
100. Koga M, Kawasaki A, Ito I, Furuya T, Ohashi J, Kyogoku C, et al. Cumulative association of eight susceptibility genes with systemic lupus erythematosus in a Japanese female population. J Hum Genet (2011) 56(7):503-7. doi:10.1038/jhg.2011.49
101. Chung SA, Brown EE, Williams AH, Ramos PS, Berthier CC, Bhangale T, et al. Lupus nephritis susceptibility loci in women with systemic lupus erythematosus. J Am Soc Nephrol (2014) 25(12):2859-70. doi:10.1681/ASN.2013050446
102. De Azevêdo Silva J, Addobbati C, Sandrin-Garcia P, Crovella S. Systemic lupus erythematosus: old and new susceptibility genes versus clinical manifestations. Curr Genomics (2014) 15(1):52-65. doi:10.2174/138920291501140306113715
103. Enevold C, Nielsen CH, Jacobsen RS, Hermansen ML, Molbo D, Avlund K, et al. Single nucleotide polymorphisms in genes encoding toll-like receptors 7, 8 and 9 in Danish patients with systemic lupus erythematosus. Mol Biol Rep (2014) 41(9):5755-63. doi:10.1007/s11033-014-3447-4
104. Salloum R, Niewold TB. Interferon regulatory factors in human lupus pathogenesis. Transl Res (2011) 157(6):326-31. doi:10.1016/j.trsl.2011.01.006
105. Tada Y, Kondo S, Aoki S, Koarada S, Inoue H, Suematsu R, et al. Interferon regulatory factor 5 is critical for the development of lupus in MRL/lpr mice. Arthritis Rheum (2011) 63(3):738-48. doi:10.1002/art.30183
106. Shen H, Panchanathan R, Rajavelu P, Duan X, Gould KA, Choubey D. Gender-dependent expression of murine Irf5 gene: implications for sex bias in autoimmunity. J Mol Cell Biol (2010) 2(5):284-90. doi:10.1093/jmcb/mjq023
107. Desnues B, Macedo AB, Roussel-Queval A, Bonnardel J, Henri S, Demaria O, et al. TLR8 on dendritic cells and TLR9 on B cells restrain TLR7-mediated spontaneous autoimmunity in C57BL/6 mice. Proc Natl Acad Sci U S A (2014) 111(4):1497-502. doi:10.1073/pnas.1314121111
108. Umiker BR, Andersson S, Fernandez L, Korgaokar P, Larbi A, Pilichowska M, et al. Dosage of X-linked Toll-like receptor 8 determines gender differences in the development of systemic lupus erythematosus. Eur J Immunol (2014) 44(5):1503-16. doi:10.1002/eji.201344282
109. Khan D, Dai R, Ansar Ahmed S. Sex differences and estrogen regulation of miRNAs in lupus, a prototypical autoimmune disease. Cell Immunol (2015) 294(2):70-9. doi:10.1016/j.cellimm.2015.01.004
110. Dai R, McReynolds S, Leroith T, Heid B, Liang Z, Ansar Ahmed S. Sex differences in the expression of lupus-associated miRNAs in splenocytes from lupus-prone NZB/WF1 mice. Biol Sex Differ (2013) 4(1):19. doi:10.1186/2042-6410-4-19
111. Markle JG, Frank DN, Mortin-Toth S, Robertson CE, Feazel LM, Rolle-Kampczyk U, et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science (2013) 339(6123):1084-8. doi:10.1126/science.1233521
112. Yurkovetskiy L, Burrows M, Khan AA, Graham L, Volchkov P, Becker L, et al. Gender bias in autoimmunity is influenced by microbiota. Immunity (2013) 39(2):400-12. doi:10.1016/j.immuni.2013.08.013