Antigen presenting cell-derived IL-6 restricts Th2-cell differentiation

Autor: Alice, Mayer, Delphine, Debuisson, Sébastien, Denanglaire, Fouad, Eddahri, Laurence, Fievez, Mélanie, Hercor, Emily, Triffaux, Muriel, Moser, Fabrice, Bureau, Oberdan, Leo, Fabienne, Andris
Rok vydání: 2014
Předmět:
Zdroj: European journal of immunology. 44(11)
ISSN: 1521-4141
Popis: 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.
Databáze: OpenAIRE