ParkinsonCanadaV1, Main, Exploration, bibRecord, 001A24

LRRK2 Is Involved in the IFN-γ Response and Host Response to Pathogens

Identifieur interne : 001A24 ( Main/Exploration ); précédent : 001A23; suivant : 001A25

LRRK2 Is Involved in the IFN-γ Response and Host Response to Pathogens

Auteurs : Agnès Gardet [États-Unis] ; Yair Benita [États-Unis] ; Chun Li [États-Unis] ; Bruce E. Sands [États-Unis] ; Isabel Ballester [États-Unis] ; Christine Stevens [États-Unis] ; Joshua R. Korzenik [États-Unis] ; John D. Rioux [Canada] ; Mark J. Daly [États-Unis] ; Ramnik J. Xavier [États-Unis] ; Daniel K. Podolsky [États-Unis]

Source :

Journal of immunology (Baltimore, Md. : 1950) [ 0022-1767 ] ; 2010.

RBID : PMC:3156100

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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3156100

DOI: 10.4049/jimmunol.1000548
PubMed: 20921534
PubMed Central: 3156100

Affiliations:

Le document en format XML

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</affiliation>
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<author><name sortKey="Xavier, Ramnik J" sort="Xavier, Ramnik J" uniqKey="Xavier R" first="Ramnik J." last="Xavier">Ramnik J. Xavier</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Center for the Study of the Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Center for the Study of the Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A3">Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A5">Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02141</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Podolsky, Daniel K" sort="Podolsky, Daniel K" uniqKey="Podolsky D" first="Daniel K." last="Podolsky">Daniel K. Podolsky</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Center for the Study of the Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Center for the Study of the Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A8">University of Texas Southwestern Medical Center, Dallas, TX 75390</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>University of Texas Southwestern Medical Center, Dallas</wicri:cityArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Journal of immunology (Baltimore, Md. : 1950)</title>
<idno type="ISSN">0022-1767</idno>
<idno type="eISSN">1550-6606</idno>
<imprint><date when="2010">2010</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P1"><italic>LRRK2</italic>
 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 <italic>LRRK2</italic>
 could be involved in immune responses. We show that <italic>LRRK2</italic>
 expression is enriched in human immune cells. <italic>LRRK2</italic>
 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, <italic>LRRK2</italic>
 expression enhances NF-κB–dependent transcription, suggesting its role in immune response signaling. Endogenous LRRK2 rapidly translocates near bacterial membranes, and knockdown of <italic>LRRK2</italic>
 interferes with reactive oxygen species production during phagocytosis and bacterial killing. These observations indicate that <italic>LRRK2</italic>
 is an IFN-γ target gene, and it might be involved in signaling pathways relevant to Crohn’s disease pathogenesis.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>Canada</li>
<li>États-Unis</li>
</country>
<region><li>Massachusetts</li>
<li>Texas</li>
</region>
</list>
<tree><country name="États-Unis"><region name="Massachusetts"><name sortKey="Gardet, Agnes" sort="Gardet, Agnes" uniqKey="Gardet A" first="Agnès" last="Gardet">Agnès Gardet</name>
</region>
<name sortKey="Ballester, Isabel" sort="Ballester, Isabel" uniqKey="Ballester I" first="Isabel" last="Ballester">Isabel Ballester</name>
<name sortKey="Ballester, Isabel" sort="Ballester, Isabel" uniqKey="Ballester I" first="Isabel" last="Ballester">Isabel Ballester</name>
<name sortKey="Benita, Yair" sort="Benita, Yair" uniqKey="Benita Y" first="Yair" last="Benita">Yair Benita</name>
<name sortKey="Benita, Yair" sort="Benita, Yair" uniqKey="Benita Y" first="Yair" last="Benita">Yair Benita</name>
<name sortKey="Benita, Yair" sort="Benita, Yair" uniqKey="Benita Y" first="Yair" last="Benita">Yair Benita</name>
<name sortKey="Daly, Mark J" sort="Daly, Mark J" uniqKey="Daly M" first="Mark J." last="Daly">Mark J. Daly</name>
<name sortKey="Daly, Mark J" sort="Daly, Mark J" uniqKey="Daly M" first="Mark J." last="Daly">Mark J. Daly</name>
<name sortKey="Gardet, Agnes" sort="Gardet, Agnes" uniqKey="Gardet A" first="Agnès" last="Gardet">Agnès Gardet</name>
<name sortKey="Korzenik, Joshua R" sort="Korzenik, Joshua R" uniqKey="Korzenik J" first="Joshua R." last="Korzenik">Joshua R. Korzenik</name>
<name sortKey="Korzenik, Joshua R" sort="Korzenik, Joshua R" uniqKey="Korzenik J" first="Joshua R." last="Korzenik">Joshua R. Korzenik</name>
<name sortKey="Li, Chun" sort="Li, Chun" uniqKey="Li C" first="Chun" last="Li">Chun Li</name>
<name sortKey="Li, Chun" sort="Li, Chun" uniqKey="Li C" first="Chun" last="Li">Chun Li</name>
<name sortKey="Li, Chun" sort="Li, Chun" uniqKey="Li C" first="Chun" last="Li">Chun Li</name>
<name sortKey="Podolsky, Daniel K" sort="Podolsky, Daniel K" uniqKey="Podolsky D" first="Daniel K." last="Podolsky">Daniel K. Podolsky</name>
<name sortKey="Podolsky, Daniel K" sort="Podolsky, Daniel K" uniqKey="Podolsky D" first="Daniel K." last="Podolsky">Daniel K. Podolsky</name>
<name sortKey="Podolsky, Daniel K" sort="Podolsky, Daniel K" uniqKey="Podolsky D" first="Daniel K." last="Podolsky">Daniel K. Podolsky</name>
<name sortKey="Sands, Bruce E" sort="Sands, Bruce E" uniqKey="Sands B" first="Bruce E." last="Sands">Bruce E. Sands</name>
<name sortKey="Sands, Bruce E" sort="Sands, Bruce E" uniqKey="Sands B" first="Bruce E." last="Sands">Bruce E. Sands</name>
<name sortKey="Stevens, Christine" sort="Stevens, Christine" uniqKey="Stevens C" first="Christine" last="Stevens">Christine Stevens</name>
<name sortKey="Stevens, Christine" sort="Stevens, Christine" uniqKey="Stevens C" first="Christine" last="Stevens">Christine Stevens</name>
<name sortKey="Xavier, Ramnik J" sort="Xavier, Ramnik J" uniqKey="Xavier R" first="Ramnik J." last="Xavier">Ramnik J. Xavier</name>
<name sortKey="Xavier, Ramnik J" sort="Xavier, Ramnik J" uniqKey="Xavier R" first="Ramnik J." last="Xavier">Ramnik J. Xavier</name>
<name sortKey="Xavier, Ramnik J" sort="Xavier, Ramnik J" uniqKey="Xavier R" first="Ramnik J." last="Xavier">Ramnik J. Xavier</name>
<name sortKey="Xavier, Ramnik J" sort="Xavier, Ramnik J" uniqKey="Xavier R" first="Ramnik J." last="Xavier">Ramnik J. Xavier</name>
</country>
<country name="Canada"><noRegion><name sortKey="Rioux, John D" sort="Rioux, John D" uniqKey="Rioux J" first="John D." last="Rioux">John D. Rioux</name>
</noRegion>
<name sortKey="Rioux, John D" sort="Rioux, John D" uniqKey="Rioux J" first="John D." last="Rioux">John D. Rioux</name>
</country>
</tree>
</affiliations>
</record>

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La maladie de Parkinson au Canada (serveur d'exploration)

LRRK2 Is Involved in the IFN-γ Response and Host Response to Pathogens

LRRK2 Is Involved in the IFN-γ Response and Host Response to Pathogens

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	La maladie de Parkinson au Canada (serveur d'exploration)
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