An increase in LRRK2 suppresses autophagy and enhances Dectin-1-induced immunity in a mouse model of colitis.

ABSTRACT: The LRRK2/MUC19 gene region constitutes a high-risk genetic locus for the occurrence of both inflammatory bowel diseases (IBDs) and Parkinson's disease. We show that dendritic cells (DCs) from patients with Crohn's disease (CD) and lymphoblastoid cell lines derived from patients without CD but bearing a high-risk allele (rs11564258) at this locus as heterozygotes exhibited increased LRRK2 expression in vitro. To investigate the immunological consequences of this increased LRRK2 expression, we conducted studies in transgenic mice overexpressing Lrrk2 and showed that these mice exhibited more severe colitis induced by dextran sodium sulfate (DSS) than did littermate control animals. This increase in colitis severity was associated with lamina propria DCs that showed increased D

SUBMITTER: Takagawa T 

PROVIDER: S-EPMC6636639 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature