“Lupoid hepatitis” in SLE patients and mice with experimental lupus

Shumyak, Stepan; Yang, Lijun; Han, Sung‐Sik; Zhuang, Haoyang; Reeves, Westley H.

doi:10.1016/j.clim.2016.07.007

Cited by 5 publications

(5 citation statements)

References 30 publications

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“…The relationship between SLE and variation in LFTs might be caused by three possibilities: (1) an overlap of SLE with another autoimmune liver disease; (2) comorbidity of SLE and a non-autoimmune hepatopathy; or (3) the existence of liver parenchymal injury that only relates to SLE (lupus hepatitis) ( 8 , 9 ). The first category, which occurs with higher incidence, is the overlapping of liver injury ascribed by autoimmune mechanisms, such as autoimmune hepatitis (AIH) or primary biliary cirrhosis, with hepatopathies triggered by SLE ( 5 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

Role of Hepatic Deposited Immunoglobulin G in the Pathogenesis of Liver Damage in Systemic Lupus Erythematosus

et al. 2018

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The onset of hepatic disorders in patients with systemic lupus erythematosus (SLE) is frequent; however, the etiology and liver pathogenesis of SLE remain unknown. In the present study, the role of hepatic deposited immunoglobulin G (IgG) in SLE-derived liver damage was investigated. From a retrospective analysis of the medical records of 404 patients with lupus and from experimental studies on mice models, we found that liver dysfunction is common in SLE and liver damage with IgG deposition spontaneously develops in lupus-prone mice. Liver injury was recreated in mice by injecting IgG from lupus serum intrahepatically. The inflammation intensity in the liver decreased with IgG depletion and the lupus IgG-induced liver inflammation in FcγRIII-deficient mice was comparatively low; while, inflammation was increased in FcγRIIb-deficient mice. Macrophages, Kupffer cells, natural killer cells, and their products, but not lymphocytes, are required for the initiation of SLE-associated liver inflammation. Blocking IgG signaling using a spleen tyrosine kinase (Syk) inhibitor suppressed the liver damage. Our findings provided evidence of spontaneously established liver damage in SLE. They also suggested that hepatic-deposited lupus IgG is an important pathological factor in the development of liver injury and that hepatic inflammation is regulated by the Syk signaling pathway. Thus, Syk inhibition might promote the development of a therapeutic strategy to control liver damage in patients with SLE.

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Section: Introductionmentioning

confidence: 99%

Role of Hepatic Deposited Immunoglobulin G in the Pathogenesis of Liver Damage in Systemic Lupus Erythematosus

et al. 2018

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“…One significant consequence of mesenteric disturbances detected in our experimental model was lupoid hepatitis. The involvement of liver typically occurs 10–11 months after the single injection of pristane and the major histological findings are coagulative necrosis, hepatocyte death, bile stasis, bile duct proliferation and lymphoplasmacytic infiltrate in peri-portal zone 50 . These histopathological aspects were observed 6 months after pristane injection in liver of Lgals3 −/− mice.…”

Section: Discussionmentioning

confidence: 99%

Galectin-3 orchestrates the histology of mesentery and protects liver during lupus-like syndrome induced by pristane

Lemos

Pereira

Carvalho

et al. 2019

Sci Rep

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Galectin-3 (Gal-3) controls intercellular and cell-extracellular matrix interactions during immunological responses. In chronic inflammation, Gal-3 is associated with fibrotic events, regulates B cell differentiation and delays lupus progression. Gal-3 deficient mice (Lgals3−/−) have intense germinal center formation and atypical plasma cell generation correlated to high levels IgG, IgE, and IgA. Here, we used pristane (2,6,10,14-tetramethylpentadecane) to induce lupus-like syndrome in Lgals3−/− and Lgals3+/+ BALB/c mice. Mesentery and peritoneal cells were monitored because promptly react to pristane injected in the peritoneal cavity. For the first time, mesenteric tissues have been associated to the pathogenesis of experimental lupus-like syndrome. In Lgals3+/+ pristane-induced mice, mesentery was hallmarked by intense fibrogranulomatous reaction restricted to submesothelial regions and organized niches containing macrophages and B lymphocytes and plasma cells. In contrast, Lgals3−/− pristane-treated mice had diffuse mesenteric fibrosis affecting submesothelium and peripheral tissues, atypical M1/M2 macrophage polarization and significant DLL1+ cells expansion, suggesting possible involvement of Notch/Delta pathways in the disease. Early inflammatory reaction to pristane was characterized by significant disturbances on monocyte recruitment, macrophage differentiation and dendritic cell (DC) responses in the peritoneal cavity of pristane-induced Lgals3−/− mice. A correlative analysis showed that mesenteric damages in the absence of Gal-3 were directly associated with severe portal inflammation and hepatitis. In conclusion, it has suggested that Gal-3 orchestrates histological organization in the mesentery and prevents lupoid hepatitis in experimental lupus-like syndrome by controlling macrophage polarization, Notch signaling pathways and DC differentiation in mesenteric structures.

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“…Various mechanisms can lead to liver injury in other models of autoimmune and autoinflammatory diseases. Systemic production of autoantibodies is associated with periportal hepatitis in a model of systemic lupus erythematosus . Steatohepatitis appears as a consequence of altered microbiota and bacterial translocation in models of ulcerative colitis .…”

Section: Discussionmentioning

confidence: 99%

“…Systemic production of autoantibodies is associated with periportal hepatitis in a model of systemic lupus erythematosus. 38 Steatohepatitis appears as a consequence of altered microbiota and bacterial translocation in models of ulcerative colitis. 39,40 Mice with collagen-induced arthritis display increased levels of oxidation products in both the serum and liver.…”

Section: Discussionmentioning

confidence: 99%

Liver fibrosis is associated with cutaneous inflammation in the imiquimod-induced murine model of psoriasiform dermatitis

et al. 2018

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“Lupoid hepatitis” in SLE patients and mice with experimental lupus

Cited by 5 publications

References 30 publications

Role of Hepatic Deposited Immunoglobulin G in the Pathogenesis of Liver Damage in Systemic Lupus Erythematosus

Role of Hepatic Deposited Immunoglobulin G in the Pathogenesis of Liver Damage in Systemic Lupus Erythematosus

Galectin-3 orchestrates the histology of mesentery and protects liver during lupus-like syndrome induced by pristane

Liver fibrosis is associated with cutaneous inflammation in the imiquimod-induced murine model of psoriasiform dermatitis

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