Attenuated liver fibrosis in the absence of B cells

Novobrantseva, Tatiana; Majeau, Gerard R.; Amatucci, Aldo; Kogan, Sophia; Brenner, Ian; Casola, Stefano; Shlomchik, Mark J.; Koteliansky, Victor; Hochman, Paula S.; Ibraghimov, Alexander

doi:10.1172/jci24798

Cited by 242 publications

(239 citation statements)

References 57 publications

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“…B cell deficiency has also been reported to attenuate liver fibrosis in a murine CCl 4 -induced liver fibrosis model. 38 Adoptive transfer of B cells into MT mice in our study resulted in a marked decrease of the tubular proliferative index of postischemic kidneys, and tubular damage and atrophy were comparable to control mice. Adoptively transferred B cells trafficked into the postischemic kidneys and differentiated into plasma cells.…”

Section: Discussionsupporting

confidence: 60%

B Cells Limit Repair after Ischemic Acute Kidney Injury

Jang

Gandolfo

Ko³

et al. 2010

Journal of the American Society of Nephrology

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Section: Discussionsupporting

confidence: 60%

B Cells Limit Repair after Ischemic Acute Kidney Injury

Jang

Gandolfo

Ko³

et al. 2010

Journal of the American Society of Nephrology

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“…60,61 The role of B cells in the pathogenesis of fibrosis was identified by the reduction in collagen deposition observed in CCl 4 -induced fibrosis in B cell-deficient mice. 62 It is possible that several mechanisms are responsible for the impact of B cells on liver fibrosis. It is speculated that B-cell production of the profibrotic cytokine IL-6 contributes to liver fibrosis through induction of HSC differentiation into myofibroblasts, fibroblast proliferation and increased collagen and TIMP synthesis.…”

Section: Innate and Adaptive Immunity In Liver Fibrosismentioning

confidence: 99%

Liver fibrosis: mechanisms of immune-mediated liver injury

2011

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Liver fibrosis and its end-stage consequence, cirrhosis, represent the final common pathway of virtually all chronic liver diseases. Research into hepatic stellate cell activation, imbalance of the extracellular matrix synthesis and degradation and the contribution of cytokines and chemokines has further elucidated the mechanisms underlying fibrosis. Furthermore, clarification of changes in host adaptive and innate immune systems has accelerated our understanding of the association between liver inflammation and fibrosis. Continued elucidation of the mechanisms of hepatic fibrosis has provided a comprehensive model of fibrosis progression and regression. This review summarizes the current concepts of improvements that have been made in the field of fibrosis.

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“…47 Finally, B lymphocytes, which comprise up to 50% of the total lymphocyte pool in liver, contribute to the fibrogenic milieu because mice lacking B cells (JH−/− animals) have attenuated fibrosis, apparently by more rapid ECM degradation after CCl 4 injury, implicating an unknown interaction with pathways of matrix degradation. 48 …”

mentioning

confidence: 99%

Mechanisms of Hepatic Fibrogenesis

2008

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Substantial improvements in the treatment of chronic liver disease have accelerated interest in uncovering the mechanisms underlying hepatic fibrosis and its resolution. Activation of resident hepatic stellate cells into proliferative, contractile, and fibrogenic cells in liver injury remains a dominant theme driving the field. However, several new areas of rapid progress in the past 5-10 years also have taken root, including: (1) identification of different fibrogenic populations apart from resident stellate cells, for example, portal fibroblasts, fibrocytes, and bone-marrow-derived cells, as well as cells derived from epithelial mesenchymal transition; (2) emergence of stellate cells as finely regulated determinants of hepatic inflammation and immunity; (3) elucidation of multiple pathways controlling gene expression during stellate cell activation including transcriptional, posttranscriptional, and epigenetic mechanisms; (4) recognition of disease-specific pathways of fibrogenesis; (5) re-emergence of hepatic macrophages as determinants of matrix degradation in fibrosis resolution and the importance of matrix cross-linking and scar maturation in determining reversibility; and (6) hints that hepatic stellate cells may contribute to hepatic stem cell behavior, cancer, and regeneration. Clinical and translational implications of these advances have become clear, and have begun to impact significantly on the management and outlook of patients with chronic liver disease.The field of hepatic fibrosis is flourishing thanks to continued experimental advances complemented by exciting progress in the treatment of chronic liver disease. 1 Control of chronic hepatitis B and C by antiviral therapies has established that advanced fibrosis can regress in association with improved clinical outcomes, 2-4 thereby intensifying enthusiasm to uncover the mechanistic basis for hepatic fibrogenesis and its attenuation. At the same time, simple paradigms defining the cellular sources of extracellular matrix (ECM), and the roles of cytokines and paracrine interactions among resident liver cells and inflammatory cells have yielded a more nuanced understanding of how the liver responds to injury. These advances have had a collateral benefit towards understanding fibrosis in other organs, particularly the pancreas. 5 Thus, a review of the mechanisms underlying hepatic fibrosis is not only timely, but is more clinically relevant than ever. This article focuses on recent advances in the field, building on established principles from earlier reviews 6,7 while weaving in their clinical relevance, but also emphasizing the molecular subtleties that have emerged through continued progress in the field. General PrinciplesFibrosis, or scarring of the liver, is a wound-healing response that engages a range of cell types and mediators to encapsulate injury. Although even acute injury will activate mechanisms of fibrogenesis, the sustained signals associated with chronic liver disease caused by infection, Cirrhosis, the most advanced stage ...

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Attenuated liver fibrosis in the absence of B cells

Cited by 242 publications

References 57 publications

B Cells Limit Repair after Ischemic Acute Kidney Injury

B Cells Limit Repair after Ischemic Acute Kidney Injury

Liver fibrosis: mechanisms of immune-mediated liver injury

Mechanisms of Hepatic Fibrogenesis

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