ORCID
- Dina Dikovskaya: 0000-0003-3161-3072
Abstract
Mutations in Leucine-Rich Repeat protein Kinase 2 (LRRK2) are associated with Parkinson’s disease (PD) and Crohn’s disease (CD), but the regulation of LRRK2 during inflammation remains relatively unexplored. Here we describe the development of a flow cytometry-based assay to assess LRRK2 activity in individual cells and the generation of an EGFP-Lrrk2 knock-in reporter mouse to analyse cell-specific LRRK2 expression. Using these tools, we measured LRRK2 levels and activity in murine splenic and intestinal immune cells and in human blood. Anti-CD3 induced inflammation increases LRRK2 expression and activity in B cells and monocytes, while in mature neutrophils, inflammation stimulates activity but reduces LRRK2 expression. A kinase-activating PD-associated LRRK2-R1441C mutation exacerbates inflammation-induced activation of LRRK2 specifically in monocytes and macrophages. We identify IL-4 as a novel T-cell-derived factor that upregulates LRRK2 expression and activity in B cells, replicating inflammatory effects observed in vivo. Our findings provide valuable new insights into the regulation of the LRRK2 pathway in immune cells, crucial for understanding LRRK2 and its therapeutic potential in inflammatory diseases such as CD.
DOI Link
Publication Date
2025-07-08
Publication Title
EMBO Reports
Volume
26
Issue
13
ISSN
1469-221X
Acceptance Date
2025-04-30
Deposit Date
2025-11-13
Additional Links
Keywords
B Cells, Crohn’s Disease, Interleukin-4, LRRK2, Parkinson’s Disease
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
First Page
3327
Last Page
3356
Recommended Citation
Dikovskaya, D., Pemberton, R., Taylor, M., Tasegian, A., Bhattacharya, P., Zeneviciute, K., Sammler, E., Howden, A., Alessi, D., & Swamy, M. (2025) 'Inflammation and IL-4 regulate Parkinson’s and Crohn’s disease associated kinase LRRK2', EMBO Reports, 26(13), pp. 3327-3356. Available at: 10.1038/s44319-025-00473-x
