Scientists may have discovered why a particular genetic mutation is associated with increased risk of Crohn's disease, a chronic inflammatory bowel disorder, as reported in a published study online in Nature Immunology this week.
Earlier studies showed that human cells bearing this mutation which interrupts the sequence of the gene encoding the pathogen detector NOD2 release lower amounts of the anti-inflammatory protein interleukin 10. However, mouse cells engineered to express a similar mutation produced normal amounts of interleukin 10.
A team led by Xiaojing Ma and colleagues now show that the human NOD2 mutant prevents activation of hnRNPA1, a protein required for expression of the human interleukin 10 gene. Notably, the human NOD2 mutant did not affect expression of the mouse interleukin 10 gene.
The findings provide insight into cellular events associated with Crohn's disease, and caution against relying solely on mouse models to investigate human immune disorders.