1. Leaky-gut enhanced lupus progression in the Fc gamma receptor-IIb deficient and pristane-induced mouse models of lupus
- Author
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Naraporn Somboonna, Arthid Thim-uam, Jiraphorn Issara-Amphorn, Piraya Chatthanathon, Asada Leelahavanichkul, Thiranut Jaroonwitchawan, Alisa Wilantho, Saowapha Surawut, Pratsanee Hiengrach, Tanapat Palaga, and Prapaporn Pisitkun
- Subjects
0301 basic medicine ,beta-Glucans ,Autoimmune diseases ,Cell ,lcsh:Medicine ,Spleen ,digestive system ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Feces ,Mice ,0302 clinical medicine ,Medical research ,medicine ,Animals ,Lupus Erythematosus, Systemic ,skin and connective tissue diseases ,lcsh:Science ,Creatinine ,Multidisciplinary ,Systemic lupus erythematosus ,Proteinuria ,biology ,Chemistry ,Terpenes ,Pristane ,Dextran Sulfate ,Receptors, IgG ,digestive, oral, and skin physiology ,lcsh:R ,medicine.disease ,Molecular biology ,Disease Models, Animal ,stomatognathic diseases ,030104 developmental biology ,medicine.anatomical_structure ,Apoptosis ,030220 oncology & carcinogenesis ,biology.protein ,Disease Progression ,Cytokines ,Female ,lcsh:Q ,medicine.symptom ,Antibody - Abstract
The influence 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 gut-microbiota alteration induced high serum anti-dsDNA immunoglobulin (Ig) as early as 30 days post-DSS 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-D-glucan (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 starvation-induced apoptosis, predominantly in FcGRIIb−/− cell, implying the influence 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.
- Published
- 2020