Liver XXXX occurs through dysregulation of MyD88-dependent innate B-cell activity.

@entity82 @entity4314 @entity39 @entity19 @entity71542 @entity3844 @entity409 @entity5 @entity1750 @entity14636 @entity11787 @entity19347 @entity10828 @entity11805 @entity1968
@entity409 mediated by activation of hepatic stellate cells (HSCs) leads to liver @entity82 . Here, we postulated that the immune regulatory properties of HSCs might promote the profibrogenic activity of B cells. @entity82 is completely attenuated in @entity4314 -treated, B cell-deficient   MT @entity19 , showing that B cells are required. The @entity1968 produced by HSCs augmented B-cell survival, plasma cell marker @entity10828 expression, and immunoglobulin G production. These activities were reversed following addition of the @entity1968 inhibitor @entity71542 . Transcriptional profiling of fibrotic liver B cells revealed increased expression of genes related to activation of nuclear factor k light chain enhancer of activated B cells, proinflammatory cytokine production, and @entity14636 signaling, suggesting that these B cells are activated and may be acting as inflammatory cells. Biological validation experiments also revealed increased activation ( @entity3844 and @entity11787 expression), constitutive immunoglobulin G production, and secretion of the proinflammatory cytokines @entity5 @entity39 factor-a, @entity1750 , and macrophage inflammatory protein-1a. Likewise, targeted deletion of B-cell-intrinsic myeloid differentiation primary response gene 88 signaling, an innate adaptor with involvement in @entity1968 signaling, resulted in reduced infiltration of migratory @entity11805 (+) dendritic cells and @entity19347 (++) monocytes and, hence, reduced liver pathology. CONCLUSION: Liver @entity82 occurs through a mechanism of HSC-mediated augmentation of innate B-cell activity. These findings highlight B cells as important "first responders" of the intrahepatic immune environment.
