EBI2 is a negative regulator of type I interferons in plasmacytoid and myeloid dendritic cells.

Epstein-Barr virus induced receptor 2 (EBI2), a Gαi-coupled G protein-coupled receptor, is a chemotactic receptor for B, T and dendritic cells (DC). Genetic studies have also implicated EBI2 as a regulator of an interferon regulatory factor 7 (IRF7)-driven inflammatory network (IDIN) associated with...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Eugene Y Chiang, Robert J Johnston, Jane L Grogan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dae4ec9125314ff48442f1cf9a32929c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:dae4ec9125314ff48442f1cf9a32929c
record_format	dspace
spelling	oai:doaj.org-article:dae4ec9125314ff48442f1cf9a32929c2021-11-18T08:40:21ZEBI2 is a negative regulator of type I interferons in plasmacytoid and myeloid dendritic cells.1932-620310.1371/journal.pone.0083457https://doaj.org/article/dae4ec9125314ff48442f1cf9a32929c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24386204/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Epstein-Barr virus induced receptor 2 (EBI2), a Gαi-coupled G protein-coupled receptor, is a chemotactic receptor for B, T and dendritic cells (DC). Genetic studies have also implicated EBI2 as a regulator of an interferon regulatory factor 7 (IRF7)-driven inflammatory network (IDIN) associated with autoimmune diseases, although the corollary in primary type I IFN-producing cells has not been reported. Here we demonstrate that EBI2 negatively regulates type I IFN responses in plasmacytoid DC (pDCs) and CD11b(+) myeloid cells. Activation of EBI2(-/-) pDCs and CD11b(+) cells with various TLR ligands induced elevated type I IFN production compared to wild-type cells. Moreover, in vivo challenge with endosomal TLR agonists or infection with lymphocytic choriomeningitis virus elicited more type I IFNs and proinflammatory cytokines in EBI2(-/-) mice compared to normal mice. Elevated systemic cytokines occurred despite impaired ability of EBI2-deficient pDCs and CD11b(+) cells to migrate from the blood to the spleen and peritoneal cavity under homeostatic conditions. As reported for other immune cells, pDC migration was dependent on the ligand for EBI2, 7α,25-dihydroxycholesterol. Consistent with a cell intrinsic role for EBI2, type I IFN-producing cells from EBI2-deficient mice expressed higher levels of IRF7 and IDIN genes. Together these data suggest a negative regulatory role for EBI2 in balancing TLR-mediated responses to foreign and to self nucleic acids that may precipitate autoimmunity.Eugene Y ChiangRobert J JohnstonJane L GroganPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e83457 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eugene Y Chiang Robert J Johnston Jane L Grogan EBI2 is a negative regulator of type I interferons in plasmacytoid and myeloid dendritic cells.
description	Epstein-Barr virus induced receptor 2 (EBI2), a Gαi-coupled G protein-coupled receptor, is a chemotactic receptor for B, T and dendritic cells (DC). Genetic studies have also implicated EBI2 as a regulator of an interferon regulatory factor 7 (IRF7)-driven inflammatory network (IDIN) associated with autoimmune diseases, although the corollary in primary type I IFN-producing cells has not been reported. Here we demonstrate that EBI2 negatively regulates type I IFN responses in plasmacytoid DC (pDCs) and CD11b(+) myeloid cells. Activation of EBI2(-/-) pDCs and CD11b(+) cells with various TLR ligands induced elevated type I IFN production compared to wild-type cells. Moreover, in vivo challenge with endosomal TLR agonists or infection with lymphocytic choriomeningitis virus elicited more type I IFNs and proinflammatory cytokines in EBI2(-/-) mice compared to normal mice. Elevated systemic cytokines occurred despite impaired ability of EBI2-deficient pDCs and CD11b(+) cells to migrate from the blood to the spleen and peritoneal cavity under homeostatic conditions. As reported for other immune cells, pDC migration was dependent on the ligand for EBI2, 7α,25-dihydroxycholesterol. Consistent with a cell intrinsic role for EBI2, type I IFN-producing cells from EBI2-deficient mice expressed higher levels of IRF7 and IDIN genes. Together these data suggest a negative regulatory role for EBI2 in balancing TLR-mediated responses to foreign and to self nucleic acids that may precipitate autoimmunity.
format	article
author	Eugene Y Chiang Robert J Johnston Jane L Grogan
author_facet	Eugene Y Chiang Robert J Johnston Jane L Grogan
author_sort	Eugene Y Chiang
title	EBI2 is a negative regulator of type I interferons in plasmacytoid and myeloid dendritic cells.
title_short	EBI2 is a negative regulator of type I interferons in plasmacytoid and myeloid dendritic cells.
title_full	EBI2 is a negative regulator of type I interferons in plasmacytoid and myeloid dendritic cells.
title_fullStr	EBI2 is a negative regulator of type I interferons in plasmacytoid and myeloid dendritic cells.
title_full_unstemmed	EBI2 is a negative regulator of type I interferons in plasmacytoid and myeloid dendritic cells.
title_sort	ebi2 is a negative regulator of type i interferons in plasmacytoid and myeloid dendritic cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/dae4ec9125314ff48442f1cf9a32929c
work_keys_str_mv	AT eugeneychiang ebi2isanegativeregulatoroftypeiinterferonsinplasmacytoidandmyeloiddendriticcells AT robertjjohnston ebi2isanegativeregulatoroftypeiinterferonsinplasmacytoidandmyeloiddendriticcells AT janelgrogan ebi2isanegativeregulatoroftypeiinterferonsinplasmacytoidandmyeloiddendriticcells
_version_	1718421473191788544

EBI2 is a negative regulator of type I interferons in plasmacytoid and myeloid dendritic cells.

Ejemplares similares