Abstract: Sustained hepatic and systemic inflammation, in particular originating from monocyte/macrophages, is a driving force for chronic liver disease progression to cirrhosis and underlies the development of multiorgan failure. Therefore, reprogramming mono-cyte/macrophage phenotype has emerged as an interesting strategy to limit inflammation during chronic liver injury. The inventors report here that a non-canonical form of autophagy, LC3-associated phagocytosis (LAP), is endogenously enhanced in blood and liver monocytes from cirrhotic patients and is negatively correlated to the levels of inflammatory markers in these patients. Pharmacological inhibition of LAP components or genetic disruption of LAP (Rubicon-deficient mice in myeloid cells), exacerbates the inflammatory signature in isolated human cirrhotic monocytes and the hepatic inflammatory profile in mice with chronic liver injury, resulting in enhanced liver fibrosis.

Abstract: Persistent inflammation is a driving force of fibrosis progression. Mucosal-Associated Invariant T (MAIT) cells are non-conventional T cells that display altered functions during chronic inflammatory diseases. Here, the inventors report a loss of circulating MAIT cells in cirrhotic patients and their hepatic accumulation in an activated phenotype within the fibrotic septa. Using two models of chronic liver injury, the inventors demonstrate that mice enriched in MAIT cells (V?19TCRTg) show exacerbated liver fibrosis and higher number of hepatic fibrogenic cells than wild type counterparts, whereas MAIT cell-deficient mice (MR1?/?mice) are resistant. The results highlight the profibrogenic functions of MAIT cells and suggest that 1 targeting MAIT cells may constitute an attractive antifibrogenic strategy during chronic liver injury.

Abstract: The present invention relates to methods, and pharmaceutical compositions for the treatment of fibrosis. In particular, the present invention relates to a method of treating fibrosis in a subject in need thereof comprising administering the subject with a therapeutically effective amount of at least one monoacylglycerol lipase (MGL) inhibitor.

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of fibrosis. In particular, the present invention relates to a method of treating fibrosis in a subject in need thereof comprising administering the subject with a therapeutically effective amount of at least one monoacylglycerol lipase (MGL) inhibitor.

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of fibrosis. In particular, the present invention relates to a method of treating fibrosis in a subject in need thereof comprising administering the subject with a therapeutically effective amount of at least one monoacylglycerol lipase (MGL) inhibitor.

Abstract: The invention relates to the use of antagonists to the CB1 receptor for the preparation of a composition for the treatment of hepatic diseases and preferably to the use of N-piperidino5 5-(4-chlorophenyl)-1-(2, 4-dichloropenyl)-4-methylpyrazole-3-carboxamide.

Abstract: The invention relates to a method for treating and/or preventing obesity and/or obesity-related disorders by administering to a subject in need thereof a selective inhibitor of cannabinoid type 2 (CB2) receptor expression.

Abstract: The invention relates to the use of antagonists to the CB1 receptor for the preparation of a composition for the treatment of hepatic diseases and preferably to the use of N-piperidino5 5-(4-chlorophenyl)-1-(2, 4-dichloropenyl)-4-methylpyrazole-3-carboxamide.

Abstract: The present invention relates to selective CB2 agonists for use in the prevention or treatment of alcoholic liver disease and particularly alcoholic hepatic steatosis and liver inflammation, and pharmaceutical composition thereof.

Abstract: The invention relates to the use of antagonists to the CB1 receptor for the preparation of a composition for the treatment of hepatic diseases and preferably to the use of N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide.

Abstract: The invention relates to a method for treating and/or preventing obesity and/or obesity-related disorders by administering to a subject in need thereof a selective inhibitor of cannabinoid type 2 (CB2) receptor expression.

Abstract: The invention relates to the use of a selective inhibitor of CB2 receptor expression and/or for the manufacture of a medicament indented for the treatment and/or the prevention of obesity and obesity-related disorders.

Abstract: Methods for treating diseases of the livers mediated by CB2 receptors are described. The methods may include administering an effective amount of a cannabinoid, an agent that activates a CB2 receptor, a composition that includes a non-selective agonist of CB2 and a selective antagonist of CB1, a composition that includes an agonist of CB2 receptors, and/or a composition that includes an up-regulator of CB2 receptors to a patient who has liver fibrosis.

Abstract: The invention relates to the use of a selective inhibitor of CB2 receptor expression and/or for the manufacture of a medicament indented for the treatment and/or the prevention of obesity and obesity-related disorders.

Abstract: Methods for treating diseases of the livers mediated by CB2 receptors are described. The methods may include administering an effective amount of a cannabinoid, an agent that activates a CB2 receptor, a composition that includes a non-selective agonist of CB2 and a selective antagonist of CB1, a composition that includes an agonist of CB2 receptors, and/or a composition that includes an up-regulator of CB2 receptors to a patient who has liver fibrosis.

Abstract: The invention relates to the use of antagonists to the CB1 receptor for the preparation of a composition for the treatment of hepatic diseases and preferably to the use of N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide.

Abstract: Methods for treating diseases of the livers mediated by CB2 receptors are described. The methods may include administering an effective amount of a cannabinoid, an agent that activates a CB2 receptor, a composition that includes a non-selective agonist of CB2 and a selective antagonist of CB1, a composition that includes an agonist of CB2 receptors, and/or a composition that includes an up-regulator of CB2 receptors to a patient who has non-alcoholic steatohepatitis.

Abstract: Methods and compositions for treating diseases mediated by CB2 receptors are disclosed, including fibrosis associated with liver injury.

Abstract: Methods and compositions for treating diseases mediated by CB2 receptors are disclosed, including fibrosis associated with liver injury.