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

J Immunol
Authors
Keywords
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.

Year of Publication
2010
Journal
J Immunol
Volume
185
Issue
9
Pages
5577-85
Date Published
2010 Nov 01
ISSN
1550-6606
URL
DOI
10.4049/jimmunol.1000548
PubMed ID
20921534
PubMed Central ID
PMC3156100
Links
Grant list
AI062773 / 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