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Lrrk2 IFN

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https://www.readbyqxmd.com/read/26067490/leucine-rich-repeat-kinase-2-lrrk2-deficiency-diminishes-the-development-of-experimental-autoimmune-uveitis-eau-and-the-adaptive-immune-response
#1
Wambui S Wandu, Cuiyan Tan, Osato Ogbeifun, Barbara P Vistica, Guangpu Shi, Samuel J H Hinshaw, Chengsong Xie, Xi Chen, Dennis M Klinman, Huaibin Cai, Igal Gery
BACKGROUND: Mutations in LRRK2 are related to certain forms of Parkinson's disease and, possibly, to the pathogenesis of Crohn's disease. In both these diseases inflammatory processes participate in the pathogenic process. LRRK2 is expressed in lymphoid cells and, interestingly, Lrrk2 (-/-) mice were reported to develop more severe experimental colitis than their wild type (WT) controls. Here, we examined the possible involvement of LRRK2 in the pathogenesis of experimental autoimmune uveitis (EAU), an animal model for human uveitis, by testing Lrrk2 (-/-) mice for their capacity to develop this experimental eye disease and related immune responses...
2015: PloS One
https://www.readbyqxmd.com/read/24873968/deficient-production-of-reactive-oxygen-species-leads-to-severe-chronic-dss-induced-colitis-in-ncf1-p47phox-mutant-mice
#2
Tiago Rodrigues-Sousa, Ana Filipa Ladeirinha, Ana Raquel Santiago, Helena Carvalheiro, Bruno Raposo, Ana Alarcão, António Cabrita, Rikard Holmdahl, Lina Carvalho, M Margarida Souto-Carneiro
BACKGROUND: Colitis is a common clinical complication in chronic granulomatous disease (CGD), a primary immunodeficiency caused by impaired oxidative burst. Existing experimental data from NADPH-oxidase knockout mice propose contradictory roles for the involvement of reactive oxygen species in colitis chronicity and severity. Since genetically controlled mice with a point-mutation in the Ncf1 gene are susceptible to chronic inflammation and autoimmunity, we tested whether they presented increased predisposition to develop chronic colitis...
2014: PloS One
https://www.readbyqxmd.com/read/24489305/a8-1-ncf1-deficient-mice-with-impaired-oxidative-bursthave-a-more-aggressive-progression-of-dextran-sulfate-sodium-dss-induced-colitis
#3
Tiago Rodrigues-Sousa, Ana Ricardo Xavier, Joana Marçal Gomes, Ana Alarcão, Lina Carvalho, Margarida Souto-Carneiro
INTRODUCTION: Intestinal Inflammatory Disease (IID) as a primary immunodeficiency depends on mutations in the NADPH oxidase complex, responsible for the production of reactive oxygen species (ROS). One of the most common clinical patterns in IID is chronic colitis. Ncf1-mutation in mice leads to deficiency in ROS, rendering them susceptible to autoimmunity. As in humans, Ncf1-mutation leads to the lack of ROS in B10. Q mice. We used these mutant mice to study how the lack of ROS influences DSS-induced colitis, its transitional recovery and a second colitis induction...
March 1, 2014: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/24479685/interferon-%C3%AE-induces-leucine-rich-repeat-kinase-lrrk2-via-extracellular-signal-regulated-kinase-erk5-in-macrophages
#4
Martin Kuss, Eleni Adamopoulou, Philipp J Kahle
The gene encoding leucine-rich repeat kinase 2 (LRRK2) comprises a major risk factor for Parkinson's disease. Recently, it has emerged that LRRK2 plays important roles in the immune system. LRRK2 is induced by interferon-γ (IFN-γ) in monocytes, but the signaling pathway is not known. Here, we show that IFN-γ-mediated induction of LRRK2 was suppressed by pharmacological inhibition and RNA interference of the extracellular signal-regulated kinase 5 (ERK5). This was confirmed by LRRK2 immunostaining, which also revealed that the morphological responses to IFN-γ were suppressed by ERK5 inhibitor treatment...
June 2014: Journal of Neurochemistry
https://www.readbyqxmd.com/read/21738687/regulation-of-lrrk2-expression-points-to-a-functional-role-in-human-monocyte-maturation
#5
Jonathan Thévenet, Rosanna Pescini Gobert, Robertus Hooft van Huijsduijnen, Christoph Wiessner, Yves Jean Sagot
Genetic variants of Leucine-Rich Repeat Kinase 2 (LRRK2) are associated with a significantly enhanced risk for Parkinson disease, the second most common human neurodegenerative disorder. Despite major efforts, our understanding of LRRK2 biological function and regulation remains rudimentary. In the present study we analyze LRRK2 mRNA and protein expression in sub-populations of human peripheral blood mononuclear cells (PBMCs). LRRK2 mRNA and protein was found in circulating CD19(+) B cells and in CD14(+) monocytes, whereas CD4(+) and CD8(+) T cells were devoid of LRRK2 mRNA...
2011: PloS One
https://www.readbyqxmd.com/read/20921534/lrrk2-is-involved-in-the-ifn-gamma-response-and-host-response-to-pathogens
#6
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
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...
November 1, 2010: Journal of Immunology: Official Journal of the American Association of Immunologists
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