The role of cholestasis in regulation of CD1d mediated bile duct inflammation.
Application to finalize ongoing project (FOTS 8210).
1. The purpose of the trial
Primary sclerosing cholangitis (PSC) is a chronic inflammatory biliary disease affecting both the intra- and extrahepatic biliary ducts in young individuals (30-40 years old). PSC patients experience an increased frequency of autoimmune conditions (25%), and inflammatory bowel disease is seen in up to 80% of the patients. At present there is no medical treatment for PSC and the disease ultimately leads to liver cirrhosis with the need for liver transplantation or early death due to liver failure or cancer.
In this project we will address these important challenges by dissecting the mechanisms that governs inflammation in the bile ducts with a specific focus on the role of cholestasis. This goal will be achieved by studies of the immune regulation in surgically induced cholestasis in different mouse models. Specifically focusing on Natural Killer T(NKT)- cells that are abundant in the liver. We will also evaluate the changes in the liver using tissue transcriptomics.
2 Moderately stressful (moderat belastningsgrad).
We expect the animals to experience a transient mild pain post surgery.
We do not expect any impairment of the animals welfare or general condition.
3. Expected utility
Charactherization of mechanisms governing inflammation in bile ducts will contribute to the understanding of the pathophysiology of cholestatic liver diseases, and ultimately lead to novel treatment options.
4 Nr of animals and species
Mus musculus, 990 animals in total.
5. 3R
The replacement option is not apllicable.
The n-value is 5 in each group, the lowest possible number to ensure trustworthy repeatability
The surgery is based upon the internal experience and experience from a large number of research groups, as this method is highly well established. Pain relief is included.
1. The purpose of the trial
Primary sclerosing cholangitis (PSC) is a chronic inflammatory biliary disease affecting both the intra- and extrahepatic biliary ducts in young individuals (30-40 years old). PSC patients experience an increased frequency of autoimmune conditions (25%), and inflammatory bowel disease is seen in up to 80% of the patients. At present there is no medical treatment for PSC and the disease ultimately leads to liver cirrhosis with the need for liver transplantation or early death due to liver failure or cancer.
In this project we will address these important challenges by dissecting the mechanisms that governs inflammation in the bile ducts with a specific focus on the role of cholestasis. This goal will be achieved by studies of the immune regulation in surgically induced cholestasis in different mouse models. Specifically focusing on Natural Killer T(NKT)- cells that are abundant in the liver. We will also evaluate the changes in the liver using tissue transcriptomics.
2 Moderately stressful (moderat belastningsgrad).
We expect the animals to experience a transient mild pain post surgery.
We do not expect any impairment of the animals welfare or general condition.
3. Expected utility
Charactherization of mechanisms governing inflammation in bile ducts will contribute to the understanding of the pathophysiology of cholestatic liver diseases, and ultimately lead to novel treatment options.
4 Nr of animals and species
Mus musculus, 990 animals in total.
5. 3R
The replacement option is not apllicable.
The n-value is 5 in each group, the lowest possible number to ensure trustworthy repeatability
The surgery is based upon the internal experience and experience from a large number of research groups, as this method is highly well established. Pain relief is included.