title: Antigen presenting cell-derived IL-6 restricts Th2-cell differentiation.
abstract: The identification of DC-derived signals orchestrating activation of Th1 and Th17 immune responses has advanced our understanding on how these inflammatory responses develop. However, whether specific signals delivered by DCs also participate in the regulation of Th2 immune responses remains largely unknown. In this study, we show that administration of antigen-loaded, IL-6-deficient DCs to naïve mice induced an exacerbated Th2 response, characterized by the differentiation of GATA-3-expressing T lymphocytes secreting high levels of IL-4, IL-5, and IL-13. Coinjection of wild type and IL-6-deficient bone marrow-derived dendritic cells (BMDCs) confirmed that IL-6 exerted a dominant, negative influence on Th2-cell development. This finding was confirmed in vitro, where exogenously added IL-6 was found to limit IL-4-induced Th2-cell differentiation. iNKT cells were required for optimal Th2-cell differentiation in vivo although their activation occurred independently of IL-6 secretion by the BMDCs. Collectively, these observations identify IL-6 secretion as a major, unsuspected, mechanism whereby DCs control the magnitude of Th2 immunity.
authors.affiliation: Laboratoire d'Immunobiologie, Institut de Biologie et de Médecine Moléculaire, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Alice
authors.initials: A
authors.lastname: Mayer
authors.forename: Delphine
authors.initials: D
authors.lastname: Debuisson
authors.forename: Sébastien
authors.initials: S
authors.lastname: Denanglaire
authors.forename: Fouad
authors.initials: F
authors.lastname: Eddahri
authors.forename: Laurence
authors.initials: L
authors.lastname: Fievez
authors.forename: Mélanie
authors.initials: M
authors.lastname: Hercor
authors.forename: Emily
authors.initials: E
authors.lastname: Triffaux
authors.forename: Muriel
authors.initials: M
authors.lastname: Moser
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bureau
authors.forename: Oberdan
authors.initials: O
authors.lastname: Leo
authors.forename: Fabienne
authors.initials: F
authors.lastname: Andris
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology; D001491:Basophils / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D050990:GATA3 Transcription Factor / Q000096:biosynthesis; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology; D010047:Ovalbumin; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D018793:Interleukin-13; D015848:Interleukin-5; D015850:Interleukin-6; D015847:Interleukin-4; D010047:Ovalbumin
keywords: Airway allergy; DCs; IL-6; Th2-cell differentiation; iNKT cells