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

Agnès Gardet, Yair Benita, Chun Li, Bruce E. Sands, Isabel Ballester, Christine Stevens, Joshua R. Korzenik, John D. Rioux, Mark J. Daly, Ramnik J. Xavier, Daniel K. Podolsky

Research output: Contribution to journalReview article

208 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5577-5585
Number of pages9
JournalJournal of Immunology
Volume185
Issue number9
DOIs
StatePublished - Nov 1 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Gardet, A., Benita, Y., Li, C., Sands, B. E., Ballester, I., Stevens, C., Korzenik, J. R., Rioux, J. D., Daly, M. J., Xavier, R. J., & Podolsky, D. K. (2010). LRRK2 is involved in the IFN-γ response and host response to pathogens. Journal of Immunology, 185(9), 5577-5585. https://doi.org/10.4049/jimmunol.1000548