title: IL-6 activated integrated BATF/IRF4 functions in lymphocytes are T-bet-independent and reversed by subcutaneous immunotherapy.
abstract: IL-6 plays a central role in supporting pathological T(H2) and T(H17) cell development and inhibiting the protective T regulatory cells in allergic asthma. T(H17) cells have been demonstrated to regulate allergic asthma in general and T-bet-deficiency-induced asthma in particular. Here we found an inverse correlation between T-bet and Il-6 mRNA expression in asthmatic children. Moreover, experimental subcutaneous immunotherapy (SIT) in T-bet((-/-)) mice inhibited IL-6, IL-21R and lung T(H17) cells in a setting of asthma. Finally, local delivery of an anti-IL-6R antibody in T-bet((-/-)) mice resulted in the resolution of this allergic trait. Noteworthy, BATF, crucial for the immunoglobulin-class-switch and T(H2),T(H17) development, was found down-regulated in the lungs of T-bet((-/-)) mice after SIT and after treatment with anti-IL-6R antibody, indicating a critical role of IL-6 in controlling BATF/IRF4 integrated functions in T(H2), T(H17) cells and B cells also in a T-bet independent fashion in allergic asthma.
authors: Laboratory of Cellular and Molecular Lung Immunology, Institute of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany.
authors: Sonja
authors: S
authors: Koch
authors: Stephanie
authors: S
authors: Mousset
authors: Anna
authors: A
authors: Graser
authors: Sarah
authors: S
authors: Reppert
authors: Caroline
authors: C
authors: Übel
authors: Cornelia
authors: C
authors: Reinhardt
authors: Theodor
authors: T
authors: Zimmermann
authors: Ralf
authors: R
authors: Rieker
authors: Hans A
authors: HA
authors: Lehr
authors: Susetta
authors: S
authors: Finotto
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000276:immunology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods; D050835:Interferon Regulatory Factors / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D053655:Receptors, Interleukin-21 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000276:immunology* / Q000378:metabolism; D000099218:Interferon Regulatory Factor-4
chemical_list: D000906:Antibodies; D050976:Basic-Leucine Zipper Transcription Factors; D050835:Interferon Regulatory Factors; D015850:Interleukin-6; D012333:RNA, Messenger; D053655:Receptors, Interleukin-21; D019947:Receptors, Interleukin-6; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4; C431772:Batf protein, mouse
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