Blocking BAFF Alleviates Hepatic Fibrosis in Schistosoma japonicum-Infected Mice

Abstract

Schistosomiasis is an immunopathogenic disease characterized by egg granuloma and fibrosis. The hepatic fibrosis of schistosomiasis is caused by the coordinated action of local immune cells, liver-resident cells and related cytokines around the eggs of the liver. B-cell-activating factor (BAFF), expressed in many cells, is an essential factor for promoting the survival, differentiation, and maturation of cells. The overexpression of BAFF is closely related to many autoimmune diseases and fibrosis, but has not been reported to play a role in liver fibrosis caused by schistosomiasis. In the study, we found that, during Schistosoma japonicum (S. japonicum) infection in mice, the level of BAFF and its receptor BAFF-R progressively increased, then decreased with the extension of infection time, which was consistent with the progression of hepatic granuloma and fibrosis. Anti-BAFF treatment attenuated the histopathological damage in the liver of infected mice. The average areas of individual granulomas and liver fibrosis in anti-BAFF treatment mice were significantly lower than those in control mice, respectively. Anti-BAFF treatment increased the IL-10, decreased IL-4, IL-6, IL-17A, TGF-β, and downregulated the antibody level against S. japonicum antigens. These results suggested that BAFF acts a strong player in the immunopathology of schistosomiasis. Anti-BAFF treatment may influence Th2 and Th17 responses, and reduce the inflammatory reaction and fibrosis of schistosomiasis liver egg granuloma. It is suggested that BAFF might be a prospective target for the development of new methods to treat schistosomiasis liver fibrosis.

B cell depletion with anti-CD20 promotes neuroprotection in a BAFF-dependent manner in mice and humans

“…However, we did not observe any alteration in T cell cytokine production in the leptomeninges in dual-treated anti-CD20/anti-BAFF mice compared to that in anti-CD20 treatment alone, suggesting that anti-BAFF treatment did not elevate inflammation. Moreover, the anti-BAFF antibody that we used (Sandy-2) has not been reported to cause tissue pathology in models of hepatic fibrosis ( 72 ), chronic colitis ( 73 ), or aortic aneurysm ( 74 ). Moreover, our orthogonal findings in humans (Fig.…”

Dysregulated Glucuronidation of Bilirubin Exacerbates Liver Inflammation and Fibrosis in Schistosomiasis Japonica through the NF-κB Signaling Pathway

“…The primary schistosomes affecting humans include Schistosoma mansoni , Schistosoma japonicum ( S. japonicum ), and Schistosoma haematobium , with S. japonicum being particularly prevalent in China [ 5 , 6 ]. S. japonicum infection primarily causes liver damage in the host [ 7 ], in which advanced schistosomiasis, a fibrosing portal hypertensive syndrome, develops after long-term repeated infection with schistosome cercariae, and the disease continues to progress in the absence of timely or complete anthelmintic treatment [ 8 , 9 ]. Complications such as liver fibrosis and ascites are significant contributors to mortality in patients with advanced schistosomiasis [ 10 ].…”