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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies / metabolism
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Asthma / genetics
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Asthma / immunology
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Asthma / metabolism
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Basic-Leucine Zipper Transcription Factors / immunology*
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Basic-Leucine Zipper Transcription Factors / metabolism
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Child
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Child, Preschool
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Female
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Humans
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Hypersensitivity / genetics
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Hypersensitivity / immunology
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Hypersensitivity / metabolism
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Immunotherapy / methods
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Interferon Regulatory Factors / immunology*
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Interferon Regulatory Factors / metabolism
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Interleukin-6 / genetics
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Interleukin-6 / immunology*
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Interleukin-6 / metabolism
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Lung / immunology
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Lung / metabolism
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Male
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Mice
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RNA, Messenger / genetics
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RNA, Messenger / immunology
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Receptors, Interleukin-21 / genetics
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Receptors, Interleukin-21 / immunology
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Receptors, Interleukin-21 / metabolism
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Receptors, Interleukin-6 / genetics
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Receptors, Interleukin-6 / immunology
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Receptors, Interleukin-6 / metabolism
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T-Box Domain Proteins / genetics
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T-Box Domain Proteins / immunology*
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T-Box Domain Proteins / metabolism
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Th17 Cells / immunology*
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Th17 Cells / metabolism
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Th2 Cells / immunology*
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Th2 Cells / metabolism
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Transcription Factors / immunology*
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Transcription Factors / metabolism
Substances
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Antibodies
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Basic-Leucine Zipper Transcription Factors
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Batf protein, mouse
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Interferon Regulatory Factors
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Interleukin-6
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RNA, Messenger
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Receptors, Interleukin-21
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Receptors, Interleukin-6
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T-Box Domain Proteins
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Transcription Factors
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interferon regulatory factor-4