Friday, October 7, 2011

The liver is essential to prevent autoimmunity

Scientists have discovered a new mechanism by which the body makes sure that the immune system does not turn against its own cells. The liver is found to be involved in the process of maintaining tolerance: making sure that immune cells tolerate the cells of the body, but will launch an immune response against anything that is foreign. What the liver seems to be doing is taking up T lymphocytes, that play a role in killing cells. These cells, named CD8+, are in a naive state when they enter the liver cell. That means, they are not yet activated, in order to become a fully-fledged killer cell. Clearing CD8+ lymphocytes in the liver appears to be essential, as blocking this process caused accumulation of the T cells, that consequently got activated and started attacking and destroying the body's own cells.

Hepatocytes, cells of the liver, are able to take up the CD8+ lymphocytes, and consequently destroy them in specialized cellular compartments that contain enzymes for degradation. The liver cells only seem to take up the T cells that need to be cleared from the body: naive T cells that have specialized in recognizing body-own molecules, which therefore are harmful. After the scientists rendered take up of CD8+ cells by the hepatocyte impossible, the T cells consequently became activated and started to kill liver cells, a manifestation of a disease called hepatitis. This highlights the protective effect of take up by liver cells.

Normally, T lymphocytes are generated in the thymus (hence the T, B lymphocytes are made in the bone marrow) where the primary tolerance mechanisms are located. Cells that are found to be autoreactive, which means, attacking body-own components, are eliminated, so only T cells remain that act against foreign matter. There are a couple of peripheral tolerance mechanisms, that make sure that whenever an autoreactive T cell is found outside the thymus, roaming the blood, it will be rendered unable to assert a harmful effect. The liver has now been identified as another peripheral tolerance mechanism.

A previous study showed that the liver is also capable of defending itself against an immune response of the body. This works in the same way: the lymphocytes are taken up by the hepatocytes and consequently degraded inside the cell. This seems to explain why liver transplantation, where the whole organ is seen as foreign by the immune system, has a higher success rate than transplantation with other organs.

Combined, the data shows that the liver has an important role in regulating the immune response, which is something we might be able to use in the future. If we unravel the exact mechanism by which hepatocytes are able to protect our body against a wrongful immune response, we may use it in new therapies to combat degradation of transplanted organs by the immune system. 

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