title: LRRK2 as a negative regulator of NFAT: implications for the pathogenesis of inflammatory bowel disease.
abstract: 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. demonstrate that: LRRK2 acts as a negative regulator of NFAT in an NRON-dependent manner; LRRK2-deficient mice exhibit increased susceptibility to the development of dextran sodium sulfate colitis, which is enhanced by NFAT translocation to the nucleus; and patients exhibiting the risk LRRK2 allele have lower LRRK2 protein levels and exhibit less inhibition of NFAT. These data support the concept that defects within innate immunity trigger a robust adaptive immune response, which results in the production of proinflammatory cytokines and the development of chronic inflammation of the gastrointestinal mucosa.
authors.affiliation: Inflammatory Bowel & Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Davis Building Room 4063, Los Angeles, CA 90048, USA.
authors.forename: Puja
authors.initials: P
authors.lastname: Vora
authors.forename: Dermot P B
authors.initials: DP
authors.lastname: McGovern