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J Immunol DOI:10.4049/jimmunol.1000548

LRRK2 is involved in the IFN-gamma response and host response to pathogens.

Publication TypeJournal Article
Year of Publication2010
AuthorsGardet, A, Benita, Y, Li, C, Sands, BE, Ballester, I, Stevens, C, Korzenik, JR, Rioux, JD, Daly, MJ, Xavier, RJ, Podolsky, DK
JournalJ Immunol
Volume185
Issue9
Pages5577-85
Date Published2010 Nov 01
ISSN1550-6606
KeywordsAnimals, B-Lymphocytes, Blotting, Western, Cell Separation, Crohn Disease, Flow Cytometry, Fluorescent Antibody Technique, Gene Expression, Gene Expression Profiling, Humans, Immunity, Innate, Interferon-gamma, Intestinal Mucosa, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Mice, Microscopy, Confocal, Mucous Membrane, NF-kappa B, Oligonucleotide Array Sequence Analysis, Protein-Serine-Threonine Kinases, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction
Abstract

LRRK2 was previously identified as a defective gene in Parkinson's disease, and it is also located in a risk region for Crohn's disease. In this study, we aim to determine whether LRRK2 could be involved in immune responses. We show that LRRK2 expression is enriched in human immune cells. LRRK2 is an IFN-γ target gene, and its expression increased in intestinal tissues upon Crohn's disease inflammation. In inflamed intestinal tissues, LRRK2 is detected in the lamina propria macrophages, B-lymphocytes, and CD103-positive dendritic cells. Furthermore, LRRK2 expression enhances NF-κB-dependent transcription, suggesting its role in immune response signaling. Endogenous LRRK2 rapidly translocates near bacterial membranes, and knockdown of LRRK2 interferes with reactive oxygen species production during phagocytosis and bacterial killing. These observations indicate that LRRK2 is an IFN-γ target gene, and it might be involved in signaling pathways relevant to Crohn's disease pathogenesis.

URLhttp://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=20921534
DOI10.4049/jimmunol.1000548
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/20921534?dopt=Abstract

Alternate JournalJ. Immunol.
PubMed ID20921534
PubMed Central IDPMC3156100
Grant ListAI062773 / AI / NIAID NIH HHS / United States
P30 DK043351-22 / DK / NIDDK NIH HHS / United States
P30 DK043351-19S2 / DK / NIDDK NIH HHS / United States
DK043351 / DK / NIDDK NIH HHS / United States
P30 DK043351-20S1 / DK / NIDDK NIH HHS / United States
R01 AI062773-03 / AI / NIAID NIH HHS / United States
R01 DK060049 / DK / NIDDK NIH HHS / United States
R01 DK060049-10 / DK / NIDDK NIH HHS / United States
P30 DK043351 / DK / NIDDK NIH HHS / United States
R01 AI062773-04 / AI / NIAID NIH HHS / United States
R01 DK083756-04 / DK / NIDDK NIH HHS / United States
R01 DK060049-08 / DK / NIDDK NIH HHS / United States
R01 DK083756-03 / DK / NIDDK NIH HHS / United States
DK83756 / DK / NIDDK NIH HHS / United States
R01 DK083756-02 / DK / NIDDK NIH HHS / United States
P30 DK043351-18 / DK / NIDDK NIH HHS / United States
R01 DK060049-09 / DK / NIDDK NIH HHS / United States
R01 AI062773-01A1 / AI / NIAID NIH HHS / United States
DK060049 / DK / NIDDK NIH HHS / United States
R01 AI062773 / AI / NIAID NIH HHS / United States
P30 DK043351-21 / DK / NIDDK NIH HHS / United States
R01 DK083756-01 / DK / NIDDK NIH HHS / United States
P30 DK043351-19S1 / DK / NIDDK NIH HHS / United States
R01 AI062773-02 / AI / NIAID NIH HHS / United States
R01 DK083756 / DK / NIDDK NIH HHS / United States
P30 DK043351-20 / DK / NIDDK NIH HHS / United States
P30 DK043351-19 / DK / NIDDK NIH HHS / United States