Researchers digging into large sets of patient genomic data have found that variants of a gene called tyrosine kinase 2 (TYK2) protect against 10 different autoimmune disorders, helping to settle a long-standing debate about its role in human disease. The findings offer a launching point for developing TYK2-targeted drugs to treat arthritis, diabetes, multiple sclerosis, colitis, and other common autoimmune disorders. Genetic variants of TYK2, a protein found in immune cells, have been previously associated with lowering the risk for some autoimmune diseases, while raising risk for others, complicating efforts to exploit it as a therapeutic target. To resolve this debate, Calliope Dendrou and colleagues harnessed large patient genomic data across multiple autoimmune disorders, patient medical records, experiments in human immune cells and mice, and protein structure analyses. The researchers pinpointed a specific variant in the TYK2 gene guards against at least 10 common conditions, including psoriasis, rheumatoid arthritis, type 1 diabetes, and lupus. This protective effect depends on just the right amount of TYK2 function to keep disease in check without impairing the immune system – a delicate balance between autoimmunity and immunodeficiency. The results open the door to designing new drugs for different autoimmune disorders that mimic the protective properties of TYK2, while minimizing potential side effects.
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