Leaky-gut enhanced lupus progression in the Fc gamma receptor-IIb defcient and pristaneinduced mouse models of lupus
ผู้เขียน :
ArthidThim-uam , Saowapha Surawut , Jiraphorn Issara-Amphorn , Thiranut Jaroonwitchawan , Pratsanee Hiengrach , PirayaChatthanathon , AlisaWilantho , Naraporn Somboonna , Tanapat Palaga , Prapaporn Pisitkun , Asada Leelahavanichkul
เผยแพร่วันที่ :
21 ม.ค. 2563
วารสารวิชาการ :
Scientific Reports
เล่มที่ :
ฉบับที่ :
หน้า :
ผู้เผยแพร่ :
Nature Publishing Group
รายละเอียด :
The infuence of gut-leakage or gut-microbiota upon lupus progression was explored in 2 lupus mouse models. Pristane, administered in 4-wk-old wild-type (WT) female mice, induced lupus characteristics at 24-wk-old similar to the lupus-onset in FcGRIIb−/− mice. Gut-microbiota alteration was induced by co-housing together with the gavage of feces from 40-wk-old FcGRIIb−/− mice (symptomatic lupus). On the other hand, gut-leakage was induced by dextran sulfate solution (DSS). DSS and gutmicrobiota alteration induced high serum anti-dsDNA immunoglobulin (Ig) as early as 30 days postDSS only in FcGRIIb−/− mice. DSS, but not gut-microbiota alteration, enhanced lupus characteristics (serum creatinine and proteinuria) in both lupus models (but not in WT) at 60 days post-DSS. Indeed, DSS induced the translocation of molecular components of gut-pathogens as determined by bacterial burdens in mesenteric lymph node (MLN), endotoxemia (gut-bacterial molecule) and serum (1→3)-β-Dglucan (BG) (gut-fungal molecule) as early as 15 days post-DSS together with enhanced MLN apoptosis in both WT and lupus mice. However, DSS induced spleen apoptosis in FcGRIIb−/− and WT mice at 30 and 60 days post-DSS, respectively, suggesting the higher impact of gut-leakage against spleen of lupus mice. In addition, macrophages preconditioning with LPS plus BG were susceptible to starvationinduced apoptosis, predominantly in FcGRIIb−/− cell, implying the infuence of gut-leakage upon cell stress. In summary, gut-leakage induced gut-translocation of organismal-molecules then enhanced the susceptibility of stress-induced apoptosis, predominantly in lupus. Subsequently, the higher burdens of apoptosis in lupus mice increased anti-dsDNA Ig and worsen lupus severity through immune complex deposition. Hence, therapeutic strategies addressing gut-leakage in lupus are interesting.
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