肠道通透性
系统性红斑狼疮
生物
肠道菌群
免疫学
自身免疫
自身抗体
少年
全身炎症
炎症
免疫球蛋白A
自身免疫性疾病
免疫系统
疾病
抗体
内科学
免疫球蛋白G
医学
遗传学
作者
Radhika Gudi,Benjamin M. Johnson,Marie‐Claude Gaudreau,Wei Sun,Lauren E. Ball,Chenthamarakshan Vasu
出处
期刊:Immunology
[Wiley]
日期:2023-11-10
卷期号:171 (2): 235-249
摘要
Abstract The incidence of systemic lupus erythematosus (SLE) is about nine times higher in women than in men, and the underlying mechanisms that contribute to this gender bias are not fully understood. Previously, using lupus‐prone (SWR × NZB)F1 (SNF1) mice, we have shown that the intestinal immune system could play a role in the initiation and progression of disease in SLE, and depletion of gut microbiota produces more pronounced disease protection in females than in males. Here, we show that the gut permeability features of lupus‐prone female SNF1 mice at juvenile ages directly correlate with the expression levels of pro‐inflammatory factors, faecal IgA abundance and nAg reactivity and the eventual systemic autoantibody levels and proteinuria onset. Furthermore, we observed that the disease protection achieved in female SNF1 mice upon depletion of gut microbiota correlates with the diminished gut inflammatory protein levels, intestinal permeability and circulating microbial DNA levels. However, faecal microbiota transplant from juvenile male and females did not result in modulation of gut inflammatory features or permeability. Overall, these observations suggest that the early onset of intestinal inflammation, systemic autoantibody production and clinical stage disease in lupus‐prone females is linked to higher gut permeability in them starting at as early as juvenile age. While the higher gut permeability in juvenile lupus‐prone females is dependent on the presence of gut microbes, it appears to be independent of the composition of gut microbiota.
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