Nature Immunol. doi:10.1038/ni.1722 (2009)

A common genetic mutation may contribute to a painful autoimmune disease by interfering with the production of the anti-inflammatory protein IL-10.

The mutation, in a gene called NOD2, is associated with up to half of all cases of Crohn's disease in the West, but how it contributes to the disease has been controversial, in part because mice with the mutation have normal IL-10 production. Xiaojing Ma at Weill Medical College of Cornell University in New York and his colleagues found that cells from patients with Crohn's disease who have the mutation produce less IL-10.

Furthermore, the mutation prevents activation of a protein called hnRNP-A1, which normally binds to a region near the IL-10 gene and stimulates its expression. The authors suggest that the altered NOD2 protein functions differently in humans and mice.