The immune system faces a delicate balancing act: It must be aggressive enough to fight infections and cancer, yet restrained enough to avoid attacking the body’s own tissues.

More than two decades ago, researchers identified a gene called FOXP3 as playing a critical role in maintaining this balance and preventing autoimmune disease—work that garnered this year’s Nobel Prize in Physiology or Medicine.

Now, scientists at Gladstone Institutes and UC San Francisco (UCSF) have mapped the intricate network of genetic switches that immune cells use to fine-tune levels of FOXP3. Their findings, published in Immunity, have important implications for developing immune therapies and address a long-standing mystery about why this gene behaves differently in humans than in mice.

Researchers have uncovered and then overcome an obstacle that has led to the failure of pioneering efforts in xenotransplantation, in which an animal kidney is transplanted into a human.

More than 800,000 Americans have late-stage kidney disease, yet only 3% receive a transplant each year, according to the U.S. Centers for Disease Control and Prevention. To boost the supply of available organs, experts are exploring the use of genetically modified pig kidneys.

The genetic changes are meant to keep the human immune system from recognizing the animal organ as foreign and attacking it to cause rejection. However, recipients’ immune reactions can still lead to organ damage and failure after the surgery.

Polygenic risk scores estimate genetic predisposition to complex diseases by combining thousands of DNA variants. Dr. Anna CF Lewis of Harvard Medical School discusses their promise for personalized medicine and the ethical challenges they raise.