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Oxysterols direct immune cell migration via EBI2.

Epstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) is a G-protein-coupled receptor that is required for humoral immune responses; polymorphisms in the receptor have been associated with inflammatory autoimmune diseases. The natural ligand for EBI2 has been unknown. Here we describe the i... Full description

Journal Title: Nature July 27, 2011, Vol.475(7357), pp.524-527
Main Author: Hannedouche, Sébastien
Other Authors: Zhang, Juan , Yi, Tangsheng , Shen, Weijun , Nguyen, Deborah , Pereira, João P , Guerini, Danilo , Baumgarten, Birgit U , Roggo, Silvio , Wen, Ben , Knochenmuss, Richard , Noël, Sophie , Gessier, Francois , Kelly, Lisa M , Vanek, Mirka , Laurent, Stephane , Preuss, Inga , Miault, Charlotte , Christen, Isabelle , Karuna, Ratna , Li, Wei , Koo, Dong-In , Suply, Thomas , Schmedt, Christian , Peters, Eric C , Falchetto, Rocco , Katopodis, Andreas , Spanka, Carsten , Roy, Marie-Odile , Detheux, Michel , Chen, Yu Alice , Schultz, Peter G , Cho, Charles Y , Seuwen, Klaus , Cyster, Jason G , Sailer, Andreas W
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1476-4687 ; DOI: 10.1038/nature10280
Link: http://search.proquest.com/docview/880135193/?pq-origsite=primo
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title: Oxysterols direct immune cell migration via EBI2.
format: Article
creator:
  • Hannedouche, Sébastien
  • Zhang, Juan
  • Yi, Tangsheng
  • Shen, Weijun
  • Nguyen, Deborah
  • Pereira, João P
  • Guerini, Danilo
  • Baumgarten, Birgit U
  • Roggo, Silvio
  • Wen, Ben
  • Knochenmuss, Richard
  • Noël, Sophie
  • Gessier, Francois
  • Kelly, Lisa M
  • Vanek, Mirka
  • Laurent, Stephane
  • Preuss, Inga
  • Miault, Charlotte
  • Christen, Isabelle
  • Karuna, Ratna
  • Li, Wei
  • Koo, Dong-In
  • Suply, Thomas
  • Schmedt, Christian
  • Peters, Eric C
  • Falchetto, Rocco
  • Katopodis, Andreas
  • Spanka, Carsten
  • Roy, Marie-Odile
  • Detheux, Michel
  • Chen, Yu Alice
  • Schultz, Peter G
  • Cho, Charles Y
  • Seuwen, Klaus
  • Cyster, Jason G
  • Sailer, Andreas W
subjects:
  • Animals–Immunology
  • Antibody Formation–Drug Effects
  • B-Lymphocytes–Drug Effects
  • Cell Line–Immunology
  • Cell Movement–Chemistry
  • Gene Expression Profiling–Pharmacology
  • Gene Expression Regulation–Chemistry
  • Humans–Immunology
  • Hydroxycholesterols–Immunology
  • Liver–Immunology
  • Mice–Immunology
  • Mice, Knockout–Immunology
  • Receptors, Cell Surface–Immunology
  • Receptors, G-Protein-Coupled–Immunology
  • Sheep–Immunology
  • T-Lymphocytes–Immunology
  • Gpr183 Protein, Human
  • Hydroxycholesterols
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • 7,25-Dihydroxycholesterol
ispartof: Nature, July 27, 2011, Vol.475(7357), pp.524-527
description: Epstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) is a G-protein-coupled receptor that is required for humoral immune responses; polymorphisms in the receptor have been associated with inflammatory autoimmune diseases. The natural ligand for EBI2 has been unknown. Here we describe the identification of 7 alpha ,25-dihydroxycholesterol (also called 7 alpha ,25-OHC or 5-cholesten-3 beta ,7 alpha ,25-triol) as a potent and selective agonist of EBI2. Functional activation of human EBI2 by 7 alpha ,25-OHC and closely related oxysterols was verified by monitoring second messenger readouts and saturable, high-affinity radioligand binding. Furthermore, we find that 7 alpha ,25-OHC and closely related oxysterols act as chemoattractants for immune cells expressing EBI2 by directing cell migration in vitro and in vivo. A critical enzyme required for the generation of 7 alpha ,25-OHC is cholesterol 25-hydroxylase (CH25H). Similar to EBI2 receptor knockout mice, mice deficient in CH25H fail to position activated B cells within the spleen to the outer follicle and mount a reduced plasma cell response after an immune challenge. This demonstrates that CH25H generates EBI2 biological activity in vivo and indicates that the EBI2-oxysterol signalling pathway has an important role in the adaptive immune response.
language: eng
source:
identifier: E-ISSN: 1476-4687 ; DOI: 10.1038/nature10280
fulltext: fulltext
issn:
  • 14764687
  • 1476-4687
url: Link


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titleOxysterols direct immune cell migration via EBI2.
creatorHannedouche, Sébastien ; Zhang, Juan ; Yi, Tangsheng ; Shen, Weijun ; Nguyen, Deborah ; Pereira, João P ; Guerini, Danilo ; Baumgarten, Birgit U ; Roggo, Silvio ; Wen, Ben ; Knochenmuss, Richard ; Noël, Sophie ; Gessier, Francois ; Kelly, Lisa M ; Vanek, Mirka ; Laurent, Stephane ; Preuss, Inga ; Miault, Charlotte ; Christen, Isabelle ; Karuna, Ratna ; Li, Wei ; Koo, Dong-In ; Suply, Thomas ; Schmedt, Christian ; Peters, Eric C ; Falchetto, Rocco ; Katopodis, Andreas ; Spanka, Carsten ; Roy, Marie-Odile ; Detheux, Michel ; Chen, Yu Alice ; Schultz, Peter G ; Cho, Charles Y ; Seuwen, Klaus ; Cyster, Jason G ; Sailer, Andreas W
contributorHannedouche, Sébastien (correspondence author) ; Hannedouche, Sébastien (record owner)
ispartofNature, July 27, 2011, Vol.475(7357), pp.524-527
identifierE-ISSN: 1476-4687 ; DOI: 10.1038/nature10280
subjectAnimals–Immunology ; Antibody Formation–Drug Effects ; B-Lymphocytes–Drug Effects ; Cell Line–Immunology ; Cell Movement–Chemistry ; Gene Expression Profiling–Pharmacology ; Gene Expression Regulation–Chemistry ; Humans–Immunology ; Hydroxycholesterols–Immunology ; Liver–Immunology ; Mice–Immunology ; Mice, Knockout–Immunology ; Receptors, Cell Surface–Immunology ; Receptors, G-Protein-Coupled–Immunology ; Sheep–Immunology ; T-Lymphocytes–Immunology ; Gpr183 Protein, Human ; Hydroxycholesterols ; Receptors, Cell Surface ; Receptors, G-Protein-Coupled ; 7,25-Dihydroxycholesterol
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descriptionEpstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) is a G-protein-coupled receptor that is required for humoral immune responses; polymorphisms in the receptor have been associated with inflammatory autoimmune diseases. The natural ligand for EBI2 has been unknown. Here we describe the identification of 7 alpha ,25-dihydroxycholesterol (also called 7 alpha ,25-OHC or 5-cholesten-3 beta ,7 alpha ,25-triol) as a potent and selective agonist of EBI2. Functional activation of human EBI2 by 7 alpha ,25-OHC and closely related oxysterols was verified by monitoring second messenger readouts and saturable, high-affinity radioligand binding. Furthermore, we find that 7 alpha ,25-OHC and closely related oxysterols act as chemoattractants for immune cells expressing EBI2 by directing cell migration in vitro and in vivo. A critical enzyme required for the generation of 7 alpha ,25-OHC is cholesterol 25-hydroxylase (CH25H). Similar to EBI2 receptor knockout mice, mice deficient in CH25H fail to position activated B cells within the spleen to the outer follicle and mount a reduced plasma cell response after an immune challenge. This demonstrates that CH25H generates EBI2 biological activity in vivo and indicates that the EBI2-oxysterol signalling pathway has an important role in the adaptive immune response.
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titleOxysterols direct immune cell migration via EBI2.
authorHannedouche, Sébastien ; Zhang, Juan ; Yi, Tangsheng ; Shen, Weijun ; Nguyen, Deborah ; Pereira, João P ; Guerini, Danilo ; Baumgarten, Birgit U ; Roggo, Silvio ; Wen, Ben ; Knochenmuss, Richard ; Noël, Sophie ; Gessier, Francois ; Kelly, Lisa M ; Vanek, Mirka ; Laurent, Stephane ; Preuss, Inga ; Miault,...
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