Lrrk2 G2019S mutation incites increased cell-intrinsic neutrophil effector functions and intestinal inflammation in a model of infectious colitis
Published August 29, 2025
Output Details
Preprint September 3, 2025
Published August 29, 2025
Description
Parkinson’s Disease (PD) is a neurodegenerative disorder often preceded by gastrointestinal dysfunction. Mutations in leucine-rich repeat kinase 2 (*LRRK2*) are known risk factors for both PD and inflammatory bowel disease (IBD), suggesting a link between PD and the gastrointestinal tract. Using single-cell RNA-sequencing and spectral flow cytometry, we demonstrated that the *Lrrk2* Gly2019Ser (G2019S) mutation is associated with an increased neutrophil presence in the colonic lamina propria during *Citrobacter rodentium* infection. This concurred with a Th17 skewing, upregulated *Il17a*, and greater colonic pathology during infection. In vitro experiments showed enhanced kinase-dependent neutrophil chemotaxis and neutrophil extracellular trap (NET) formation in *Lrrk2* G2019S mice compared to wild-type counterparts. Our results add to the understanding of LRRK2-driven immune cell dysregulation and its contribution to PD, offering insights into potential biomarkers for early diagnosis and intervention in PD.
Identifier (DOI)
10.1038/s41531-025-01077-x
