LRRK2 NFAT

Inflammatory bowel disease encompasses two chronic, complex relapsing diseases believed to be caused by an excessive and poorly controlled immune response to the intestinal microbiota. The advent of genome-wide association scans has allowed for rapid identification of multiple susceptibility genes for Crohn's disease and ulcerative colitis. A locus containing LRRK2 and MUC19 is a confirmed Crohn's disease susceptibility locus. This genetic association precipitates an important functional study in which Liu et al...

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Leucine-rich repeat kinase 2 (LRRK2) has been identified by genome-wide association studies as being encoded by a major susceptibility gene for Crohn's disease. Here we found that LRRK2 deficiency conferred enhanced susceptibility to experimental colitis in mice. Mechanistic studies showed that LRRK2 was a potent negative regulator of the transcription factor NFAT and was a component of a complex that included the large noncoding RNA NRON (an NFAT repressor). Furthermore, the risk-associated allele encoding LRRK2 Met2397 identified by a genome-wide association study for Crohn's disease resulted in less LRRK2 protein post-translationally...