Gender-dependent expression of murine Irf5 gene: implications for sex bias in autoimmunity.
Molecular mechanisms that contribute to sex bias in the development of systemic lupus erythematosus (SLE), an autoimmune disease, remain unknown. We found that the expression levels of interferon regulatory factor 5 (IRF5), a lupus susceptibility factor, depend on gender of mice. We found that steady-state levels of the Irf5 mRNA were relatively higher in splenic cells from certain autoimmune-prone mice (for example, NZB and NZB/W F(1)) than in non-autoimmune C57BL/6 mice. Additionally, levels of Irf5 mRNA and protein were higher in females than in strain and age-matched males. Accordingly, splenic cells from estrogen receptor-alpha (ERα) knockout, when compared with the wild-type (ERα(+/+)), female mice expressed relatively lower levels of Irf5 mRNA and the treatment of splenic cells with 17β-estradiol increased the levels. Furthermore, splenic B cells from the female mice had relatively more IRF5 protein in the nucleus than the male mice. Collectively, our observations demonstrate a gender bias in the expression and sub-cellular localization of the murine IRF5.
Shen
Hui
H
Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45267, USA.
Panchanathan
Ravichandran
R
Rajavelu
Priya
P
Duan
Xin
X
Gould
Karen A
KA
Choubey
Divaker
D
D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D012737:Sex Factors
D050835:Interferon Regulatory Factors; C498178:Irf5 protein, mouse
Genes Immun. 2008 Jan;9(1):47-56
18046341
Trends Mol Med. 2010 Feb;16(2):47-57
20138006
Arthritis Rheum. 2010 Feb;62(2):562-73
20112383
Cell. 1996 May 3;85(3):303-6
8616885
Cytokine Growth Factor Rev. 1996 Jun;7(1):11-7
8864350
Clin Immunol. 2007 May;123(2):219-26
17336162
Nat Genet. 2006 May;38(5):550-5
16642019
Mol Cell Biol. 2008 Dec;28(24):7296-308
18824541
Clin Immunol. 2008 Aug;128(2):259-68
18514033
Curr Opin Immunol. 2004 Dec;16(6):787-93
15511674
Curr Opin Rheumatol. 2007 Sep;19(5):414-20
17762604
J Immunol. 2010 Apr 15;184(8):4051-2; author reply 4052
20368282
Arthritis Rheum. 2007 Nov;56(11):3770-83
17968932
J Biol Chem. 2005 Apr 29;280(17):17005-12
15695821
Curr Top Microbiol Immunol. 2006;305:67-88
16724801
J Biol Chem. 2001 Jun 29;276(26):23382-90
11303025
Immunity. 2006 Sep;25(3):383-92
16979570
Nature. 2005 Mar 10;434(7030):243-9
15665823
J Immunol. 2007 Jun 1;178(11):6876-85
17513736
Genes Immun. 2007 Dec;8(8):653-62
17882225
Genes Immun. 2007 Oct;8(7):590-603
17728792
Annu Rev Immunol. 2005;23:307-36
15771573
J Immunol. 2009 Dec 1;183(11):7031-8
19890043
J Interferon Cytokine Res. 2002 Jan;22(1):59-71
11846976
Mol Endocrinol. 2003 Jun;17(6):1039-53
12624116
J Immunol. 2010 Jan 15;184(2):796-806
20007534
Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4664-8
20176957
Autoimmunity. 2007 Sep;40(6):470-81
17729041
Nat Immunol. 2001 Sep;2(9):777-80
11526384
J Biol Chem. 2005 Jun 3;280(22):21078-90
15805103
Genes Immun. 2009 Jul;10(5):373-9
19440199
J Biol Chem. 2003 May 9;278(19):16630-41
12600985
Nat Immunol. 2010 Feb;11(2):114-20
20084069
J Immunol. 2001 Aug 15;167(4):1886-90
11489967
Int Immunopharmacol. 2001 Jun;1(6):1009-24
11407298
Arthritis Rheum. 2008 Aug;58(8):2481-7
18668568
Autoimmunity. 2007 Dec;40(8):591-601
18075793
Autoimmun Rev. 2007 Jun;6(6):366-72
17537382
J Biol Chem. 2008 May 23;283(21):14295-308
18332133
Mol Cell Biol. 2002 Aug;22(16):5721-40
12138184
Genes Immun. 2008 Mar;9(2):137-52
18200028
J Exp Med. 1978 Jun 1;147(6):1568-83
308087