Sex-based differences in anti-viral immunity and SLE

抗病毒免疫力和系统性红斑狼疮的性别差异

• 批准号: 6750024
• 负责人: SALLY R. SARAWAR
• 金额: $ 27.3万
• 依托单位: TORREY PINES INST FOR MOLECULAR STUDIES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-15 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6750024
• 关键词: B lymphocyte; Gammaherpesvirinae; Herpesviridae disease; T lymphocyte; autoantibody; cytokine; disease /disorder model; gender difference; gene expression; genetic susceptibility; laboratory mouse; leukocyte activation /transformation; microarray technology; microorganism immunology; sex hormones; systemic lupus erythematosus

DESCRIPTION (provided by applicant): SLE is a prevalent autoimmune disease with a significantly higher incidence in females than in males. Studies on the etiology of SLE indicate that both genetic and environmental factors influence disease penetrance. A strong correlation between SLE and previous infection with Epstein Barr virus (EBV), but not with other viruses has been reported. However, some studies have failed to find evidence of a viral etiology for SLE. This may be due to the high prevalence of EBV infection, unknown host/virus parameters, and the fact that multiple genetic loci control susceptibility to SLE. New Zealand mice are susceptible to SLE, and genetic loci that control disease susceptibility in these mice have been identified. C57/BL6 congenic mouse strains carrying one or more of three of the susceptibility loci designated Sle 1, 2, and 3 have been generated. It has been shown that the presence of at least two loci is necessary for high disease penetrance. We propose that a mouse viral homologue of EBV could substitute for the presence of a second locus, and could trigger disease in mice congenic for a single locus. We also suggest that this effect may differ in males and females, due, in part, to the more vigorous response to infection in the latter. We have a mouse model of gammaherpesvirus infection, which closely resembles EBV infection in humans and, like EBV, is able to induce non-specific B cell activation and autoantibody production, but does not induce overt autoimmune disease in C57BL/6 mice. Therefore, infection of the congenic mice with mouse gammaherpesvirus (MHV-68) may provide a useful model in which to test our hypothesis and to dissect mechanisms by which viruses can trigger autoimmune disease. In the present study, we will determine whether there are sex-based differences in the immune response to MHV-68 infection. We will determine whether infection of susceptible mice, bearing one or more Sle susceptibility locus, with MHV-68 can induce or exacerbate autoimmune disease and whether this effect differs in male and female mice. We will also determine whether there are genes whose expression is similarly modified by the presence of disease loci and the viral infection and whether their expression correlates with the induction of autoimmune disease.

描述（由申请人提供）：SLE是一种常见的自身免疫性疾病