LRRK2 Is Involved in the IFN-γ Response and Host Response to Pathogens
| Autor: | Isabel Ballester, Ramnik J. Xavier, Joshua R. Korzenik, John D. Rioux, Christine Stevens, Chun Li, Daniel K. Podolsky, Yair Benita, Mark J. Daly, Bruce E. Sands, Agnes Gardet |
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| Rok vydání: | 2010 |
| Předmět: |
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Western Immunology Fluorescent Antibody Technique Gene Expression Inflammation Cell Separation Protein Serine-Threonine Kinases Biology Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Article Pathogenesis Interferon-gamma Mice Immune system Crohn Disease Intestinal mucosa medicine Animals Humans Immunology and Allergy Intestinal Mucosa Oligonucleotide Array Sequence Analysis B-Lymphocytes Gene knockdown Microscopy Confocal Mucous Membrane Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling NF-kappa B Flow Cytometry LRRK2 Immunity Innate nervous system diseases Gene expression profiling Signal transduction medicine.symptom Signal Transduction |
| Zdroj: | The Journal of Immunology. 185:5577-5585 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1000548 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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