Compound protects transplanted hearts from rejection | Cornell Chronicle


ByJoseph BonnerDr. Jamil Azzi/Brigham and Women’s Hospital
The left image shows a section of a transplanted heart in a mouse that was given only CTLA4-Ig, a standard anti-rejection therapy. A large number of infiltrating immune cells are visible by their blue-staining nuclei, showing that the heart is undergoing rejection. Heart muscle cell nuclei are also stained blue. The right image shows a section of a transplanted heart in a mouse given CTLA4-Ig together with the immunoproteasome inhibitor DPLG3. The heart looks normal. There are almost no immune cells, only nuclei of heart muscle.
An experimental drug that blocks the activation of an immune cell component effectively prevented rejection of heart transplants in mice, according to new research from scientists at Weill Cornell Medicine and Brigham and Women’s Hospital.
The findings, published Dec. 12 in Proceedings of the National Academy of Sciences, describe a compound developed by Weill Cornell Medicine investigators that inhibits cellular structures called immunoproteasomes while sparing closely related structures called constitutive proteasomes. Proteasomes help cells regulate their behavior by breaking down regulatory proteins. Constitutive proteasomes are found in all cells, while immunoproteasomes are expressed chiefly in cells of the immune system.

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