| Four-and-a-half LIM domain protein 2 is a novel regulator of sphingosine 1-phosphate receptor 1 in CCL19-induced dendritic cell migration. | |
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MedLine Citation:
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PMID: 20592280 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We identified the four-and-a-half LIM domain protein 2 (FHL2) as a novel regulator of CCL19-induced dendritic cell (DC) migration. Initiation of migration is a hallmark of DC function and plays a central role in the induction and regulation of immune responses. In vivo, DCs continuously acquire Ag in the periphery and migrate to draining lymph nodes, under the influence of local environmental chemotactic factors like CCL19/21 or sphingosine 1-phosphate (S1P). We investigated the role of S1P- and RhoA-regulated FHL2 in this process. We found reduced nuclear localization of FHL2 in mature bone marrow-derived DCs (BMDCs), compared with immature BMDCs, following stimulation with CCL19. Furthermore, in vitro-generated murine FHL2(-/-) BMDCs displayed a significantly increased migratory speed, directionality, and migratory persistence toward the chemokine CCL19 compared with wild-type BMDCs. Moreover, in vivo, FHL2(-/-) BMDCs showed increased migration toward lymphoid organs. FHL2(-/-) BMDCs increased the expression of S1PR1, which was associated with greater Rac activation. An S1PR1 antagonist and knock-down of S1PR1 abrogated the increased migratory speed of FHL2(-/-) BMDCs. Our results identify FHL2 as an important novel regulator of DC migration via regulation of their sensitivity toward environmental migratory cues like S1P and CCL19. |
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Authors:
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Katharina König; Linda Diehl; Ursula Rommerscheidt-Fuss; Carsten Golletz; Thomas Quast; Philip Kahl; Waldemar Kolanus; Percy Knolle; Reinhard Buettner; Lukas C Heukamp |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-30 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-27 Completed Date: 2010-09-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 1466-75 Citation Subset: AIM; IM |
Affiliation:
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Institute of Pathology, University Hospital Bonn, Sigmund-Freud-Strasse 25, Bonn 53127, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bone Marrow Cells / enzymology, immunology, metabolism Cell Differentiation / genetics, immunology Cell Movement / genetics, immunology* Cell Nucleus / genetics, immunology, metabolism Cells, Cultured Chemokine CCL19 / physiology* Dendritic Cells / cytology*, enzymology, immunology* Homeodomain Proteins / genetics, physiology* Immunophenotyping Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Muscle Proteins / deficiency, genetics, physiology* Receptors, Lysosphingolipid / metabolism*, physiology Signal Transduction / genetics, immunology Transcription Factors / deficiency, genetics, physiology* Up-Regulation / genetics, immunology rac GTP-Binding Proteins / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Ccl19 protein, mouse; 0/Chemokine CCL19; 0/Fhl2 protein, mouse; 0/Homeodomain Proteins; 0/Muscle Proteins; 0/Receptors, Lysosphingolipid; 0/S1PR1 protein, human; 0/Transcription Factors; EC 3.6.5.2/rac GTP-Binding Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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