LRRK2 as a negative regulator of NFAT: Implications for the pathogenesis of inflammatory bowel disease

Expert Review of Clinical Immunology

Volumn 8, Issue 3, 2012, Pages 227-229

  Vora, Puja ^a,b   McGovern, Dermot P B ^a  

^a CEDARS SINAI MEDICAL CENTER   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Crohns disease; innate immunity; LRRK2; NFAT; ulcerative colitis

Indexed keywords

CYCLOSPORIN A; DEXTRAN SULFATE; INTERLEUKIN 12; INTERLEUKIN 12P40; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 6; LEUCINE RICH REPEAT KINASE 2; MUCIN; MUCIN 19; TACROLIMUS; TRANSCRIPTION FACTOR NFAT; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG;

ADAPTIVE IMMUNITY; ALLELE; CELL NUCLEUS; COLITIS; CROHN DISEASE; CYTOKINE PRODUCTION; ENTERITIS; GENE LOCATION; GENE LOCUS; GENE TRANSLOCATION; GENETIC ASSOCIATION; GENETIC RISK; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HEMATOCHEZIA; HUMAN; INNATE IMMUNITY; NONHUMAN; PATHOGENESIS; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; ULCERATIVE COLITIS; WEIGHT REDUCTION;

EID: 84858397791     PISSN: 1744666X     EISSN: 17448409     Source Type: Journal    
DOI: 10.1586/eci.12.11     Document Type: Review

References (16)

1. Anderson CA, Boucher G, Lees CW et al. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat. Genet. 43(3), 246-252 (2011).
2. Franke A, Mcgovern DP, Barrett JC et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat. Genet. 42(12), 1118-1125 (2010).
3. Vora P, Shih DQ, Mcgovern DP, Targan SR. Current concepts on the immunopathogenesis of inflammatory bowel disease. Front. Biosci. E4, 1451-1477 (2012).
4. Shih DQ, Targan SR, Mcgovern D. Recent advances in IBD pathogenesis: genetics and immunobiology. Curr. Gastroenterol. Rep. 10(6), 568-575 (2008).
5. Crabtree GR, Olson EN. NFAT signaling: Choreographing the social lives of cells. Cell 109 (Suppl.) S67-S79 (2002).
6. Willingham AT, Orth AP, Batalov S et al. A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science 309(5740), 1570-1573 (2005).
7. Zimprich A, Biskup S, Leitner P et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44(4), 601-607 (2004).
8. Umeno J, Asano K, Matsushita T et al. Meta-analysis of published studies identified eight additional common susceptibility loci for Crohn's disease and ulcerative colitis. Inflamm. Bowel Dis. 17(12), 2407-2415 (2011).
9. Barrett JC, Hansoul S, Nicolae DL et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat. Genet. 40(8), 955-962 (2008).
10. Zhang FR, Huang W, Chen SM et al. Genome-wide association study of leprosy. N. Engl. J. Med. 361(27), 2609-2618 (2009).
11. Liu Z, Lee J, Krummey S, Lu W, Cai H, Lenardo MJ. The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease. Nat. Immunol. 12(11), 1063-1070 (2011).
12. Gardet A, Benita Y, Li C et al. LRRK2 is involved in the IFN-gamma response and host response to pathogens. J. Immunol. 185(9), 5577-5585 (2010).
13. Sommerer C, Meuer S, Zeier M, Giese T. Calcineurin inhibitors and NFAT-regulated gene expression. Clin. Chim. Acta doi:10.1016/j.cca.2011.09.041 (2011) (Epub ahead of print).
14. Gomez-Suaga P, Luzon-Toro B, Churamani D et al. Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP. Hum. Mol. Genet. doi:10.1093/hmg/ddr481 (2011) (Epub ahead of print).
15. Tong Y, Yamaguchi H, Giaime E et al. Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of alpha-synuclein, and apoptotic cell death in aged mice. Proc. Natl Acad. Sci. USA 107(21), 9879-9884 (2010).
16. Alegre-Abarrategui J, Christian H, Lufino MM et al. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. Hum. Mol. Genet. 18(21), 4022-4034 (2009).