title: Antigen-presenting cell-derived IL-6 restricts the expression of GATA3 and IL-4 by follicular helper T cells.
abstract: Follicular helper T cells (Tfh) support high-affinity Ab production by germinal center B cells through both membrane interactions and secretion of IL-4 and -21, two major cytokines implicated in B-cell survival and Ab class switch. Tfh-2 cells recently emerged in humans as a strong IL-4 producer Tfh cell subset implicated in both autoimmune and allergic diseases. Although the molecular mechanisms governing Tfh cell differentiation from naive T cells have been widely described, much less is known about the regulation of cytokine secretion by mouse Tfh-2 cells. The purpose of our study was to evaluate the role of dendritic cell-derived IL-6 in fine-tuning cytokine secretion by Tfh cells. Our results demonstrate that priming of Th cells by IL-6-deficient antigen-presenting dendritic cells preferentially leads to accumulation of a subset of Tfh cells characterized by high expression of GATA3 and IL-4, associated with reduced production of IL-21. STAT3-deficient Tfh cells also overexpress GATA3, suggesting that early IL-6/STAT3 signaling during Tfh cell development inhibits the expression of a set of genes associated with the Th2 differentiation program. Overall, our data indicate that IL-6/STAT3 signaling restrains the expression of Th2-like genes in Tfh cells, thus contributing to the control of IgE secretion in vivo.
authors.affiliation: Laboratoire d'Immunobiologie, Université Libre de Bruxelles, Belgium.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Hercor
authors.affiliation: Laboratoire d'Immunobiologie, Université Libre de Bruxelles, Belgium.
authors.forename: Maelle
authors.initials: M
authors.lastname: Anciaux
authors.affiliation: Laboratoire d'Immunobiologie, Université Libre de Bruxelles, Belgium.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Denanglaire
authors.affiliation: Laboratoire d'Immunobiologie, Université Libre de Bruxelles, Belgium.
authors.forename: Delphine
authors.initials: D
authors.lastname: Debuisson
authors.affiliation: Laboratoire d'Immunobiologie, Université Libre de Bruxelles, Belgium.
authors.forename: Oberdan
authors.initials: O
authors.lastname: Leo
authors.affiliation: Laboratoire d'Immunobiologie, Université Libre de Bruxelles, Belgium.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Andris
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D020869:Gene Expression Profiling; D007114:Immunization; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000941:Antigens; D050990:GATA3 Transcription Factor; D015850:Interleukin-6; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D014157:Transcription Factors; D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E
keywords: STAT3; Tfh-2; humoral response