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Biological Chemistry

What triggers organ transplant rejection?

Differences in cell receptor between donor and host tissue set rejection in motion, study finds

by Celia Henry Arnaud
June 26, 2017 | A version of this story appeared in Volume 95, Issue 26

About half of all transplanted organs get rejected by the body within 10 years. To improve this acceptance rate, researchers want to figure out what triggers the rejection process.

Scientists already know that the adaptive immune system, made up of specialized cells such as B cells, is responsible for recognizing and attacking foreign tissue and invaders. But this system is activated by the less-specialized innate immune system, which is less well understood.

A team led by Fadi G. Lakkis of the University of Pittsburgh and Jayne S. Danska of the University of Toronto has now identified a key cell receptor in the innate immune response to tissue grafts (Sci. Immunol. 2017, DOI: 10.1126/sciimmunol.aam6202).

To find the receptor protein, the researchers studied mice genetically engineered to lack an adaptive immune system. By using a genetic mapping method called positional cloning, the team found that the animals’ innate immune response to a tissue graft depended on signal regulatory protein α (SIRPα), a receptor found on the surface of many cells.

The researchers observed that if SIRPα in graft tissue differs from SIRPα in the animals’ own tissues, the innate immune system senses CD47, the receptor’s ligand, bind more tightly to the graft tissue version of the receptor and initiates the rejection response.

“It will be interesting to see if this translates to humans and if the innate or adaptive immune response contributes more to accelerated rejection,” says Neil L. Kelleher of Northwestern University, who is using mass spectrometry to identify protein markers of transplant rejection.


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