Researchers Have Identified Why Our Bodies Reject Transplanted Organs

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Researchers have identified a previously hidden link between our immune system and the activation of cells that lead to organ rejection.

The discovery opens the way for scientists to develop new forms of treatment that could prevent immune responses from attacking life-saving tissue transplants without leaving the body so open to infection or cancer.

A type of receptor on bone marrow cells called signal regulatory protein alpha (SIRPα) has been identified by scientists from the University of Pittsburgh as the body’s watchdog responsible for dispatching the lymphocytes that target and destroy foreign cells.

In simple terms, whenever we take cells from another person’s body and put them into our own, white blood cells see them as foreign and attempt to break them apart.

Not only is this bad news for the transplanted tissues, the swelling and fever that comes with the immune response isn’t exactly a picnic either.

The mechanisms behind the white blood cell assault are fairly well understood – molecules on the outside of the cells belonging to what’s called the major histocompatibility complex (MHC) identify them as different.

A type of white blood cell called a T lymphocyte has receptors on its surface capable of recognising unknown MHC proteins and responds by attempting to break up the foreign material they’re attached to.

Lymphocytes aren’t born knowing what’s foreign and what’s not; they need to be taught. Which is the job of another part of the immune system called a dendritic cell.

Dendritic cells chew up foreign proteins and weave them into their own MHC before displaying them on their surface like a microscopic ‘wanted’ poster. They then migrate into the body’s lymph nodes where they interact with the gun-slinging T lymphocytes.

Exactly how dendritic cells identify foreign materials, however, has been something of a mystery.

To learn more, the researchers studied the transplanted tissues in mice engineered to lack certain white blood cells such as their T lymphocytes.

They found that differences between the mice donor’s and recipient’s SIRPα gene correlated with the recipient’s immune responses.

SIRPα isn’t an unknown protein, already understood to bind to another protein called CD47 that triggers a range of immune responses in different white blood cells.

Joining the dots, the researchers believe CD47 on monocytes – the white blood cells that grow into dendritic cells – interact with SIRPα receptors on foreign tissues, setting off the entire ID check process.

“Once these cells are activated, then they turn around and activate the rest of the immune system, and that leads to the full-blown rejection of the organ,” lead researcher Fadi Lakkis from the University of Pittsburgh told Liz Reid at 90.5 WESA.

“What we would like to do is sequence the SIRP-alpha gene in many humans who are donors and recipients of organ or bone marrow, and then ask whether a mismatch affects the outcome after transplantation.”

A better match between the donor’s and recipient’s SIRPα genes could help reduce the risk of the immune response being sparked in the first place.

Take a look at the video clip below to get a better idea of how the process is thought to work.

Even when organs are chosen to have closely matching MHC proteins, subtle differences can still produce immune responses. For example, one in 10 hearts and nearly one in 20 kidneys will show signs of being rejected by the body within the first year in spite of being declared compatible.

To avoid rejection, organ recipients need to be on treatments that suppress the immune system, not only making them prone to infection and cancer but often raising the risk of heart attacks and strokes by increasing blood pressure.

New treatments focussing on SIRPα might help reduce the doses or types of medications, and possibly help prolong the organ’s life.

This research was published in Science Immunology.

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