Aryl hydrocarbon receptor is required for optimal B-cell proliferation

Matteo Villa, Manolis Gialitakis, Mauro Tolaini, Helena Ahlfors, Colin J. Henderson, C. Roland Wolf, Robert Brink, Brigitta Stockinger (Lead / Corresponding author)

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    Abstract

    The aryl hydrocarbon receptor (AhR), a transcription factor known for mediating xenobiotic toxicity, is expressed in B cells, which are known targets for environmental pollutants. However, it is unclear what the physiological functions of AhR in B cells are. We show here that expression of Ahr in B cells is up-regulated upon B-cell receptor (BCR) engagement and IL-4 treatment. Addition of a natural ligand of AhR, FICZ, induces AhR translocation to the nucleus and transcription of the AhR target gene Cyp1a1, showing that the AhR pathway is functional in B cells. AhR-deficient (Ahr(-/-)) B cells proliferate less than AhR-sufficient (Ahr(+/+)) cells following in vitro BCR stimulation and in vivo adoptive transfer models confirmed that Ahr(-/-) B cells are outcompeted by Ahr(+/+) cells. Transcriptome comparison of AhR-deficient and AhR-sufficient B cells identified cyclin O (Ccno), a direct target of AhR, as a top candidate affected by AhR deficiency.

    Original languageEnglish
    Pages (from-to)116-128
    Number of pages13
    JournalEMBO Journal
    Volume36
    Issue number1
    Early online date14 Nov 2016
    DOIs
    Publication statusPublished - 4 Jan 2017

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    Aryl Hydrocarbon Receptors
    Cell proliferation
    B-Lymphocytes
    Cell Proliferation
    Cells
    Interleukin-4 Receptors
    Environmental Pollutants
    Cyclins
    Adoptive Transfer
    Xenobiotics
    Transcription
    Transcriptome
    Toxicity
    Transcription Factors

    Cite this

    Villa, Matteo ; Gialitakis, Manolis ; Tolaini, Mauro ; Ahlfors, Helena ; Henderson, Colin J. ; Wolf, C. Roland ; Brink, Robert ; Stockinger, Brigitta. / Aryl hydrocarbon receptor is required for optimal B-cell proliferation. In: EMBO Journal. 2017 ; Vol. 36, No. 1. pp. 116-128.
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    abstract = "The aryl hydrocarbon receptor (AhR), a transcription factor known for mediating xenobiotic toxicity, is expressed in B cells, which are known targets for environmental pollutants. However, it is unclear what the physiological functions of AhR in B cells are. We show here that expression of Ahr in B cells is up-regulated upon B-cell receptor (BCR) engagement and IL-4 treatment. Addition of a natural ligand of AhR, FICZ, induces AhR translocation to the nucleus and transcription of the AhR target gene Cyp1a1, showing that the AhR pathway is functional in B cells. AhR-deficient (Ahr(-/-)) B cells proliferate less than AhR-sufficient (Ahr(+/+)) cells following in vitro BCR stimulation and in vivo adoptive transfer models confirmed that Ahr(-/-) B cells are outcompeted by Ahr(+/+) cells. Transcriptome comparison of AhR-deficient and AhR-sufficient B cells identified cyclin O (Ccno), a direct target of AhR, as a top candidate affected by AhR deficiency.",
    author = "Matteo Villa and Manolis Gialitakis and Mauro Tolaini and Helena Ahlfors and Henderson, {Colin J.} and Wolf, {C. Roland} and Robert Brink and Brigitta Stockinger",
    note = "This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, The UK Medical Research Council and the Wellcome Trust. We would like to acknowledge the animal facility for expert management of breeding and maintenance of our mice as well as support by the Flow Cytometry facility and the Sequencing Facility. This work was funded by a Boehringer Ingelheim Fonds PhD Fellowship to M.V., a Wellcome Investigator Grant to B.S. and Cancer Research Programme Grant C4639/ A10822 to C.J.H. and C.R.W.",
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    Villa, M, Gialitakis, M, Tolaini, M, Ahlfors, H, Henderson, CJ, Wolf, CR, Brink, R & Stockinger, B 2017, 'Aryl hydrocarbon receptor is required for optimal B-cell proliferation', EMBO Journal, vol. 36, no. 1, pp. 116-128. https://doi.org/10.15252/embj.201695027

    Aryl hydrocarbon receptor is required for optimal B-cell proliferation. / Villa, Matteo; Gialitakis, Manolis; Tolaini, Mauro; Ahlfors, Helena; Henderson, Colin J.; Wolf, C. Roland; Brink, Robert; Stockinger, Brigitta (Lead / Corresponding author).

    In: EMBO Journal, Vol. 36, No. 1, 04.01.2017, p. 116-128.

    Research output: Contribution to journalArticle

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    AU - Gialitakis, Manolis

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    AU - Wolf, C. Roland

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    AU - Stockinger, Brigitta

    N1 - This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, The UK Medical Research Council and the Wellcome Trust. We would like to acknowledge the animal facility for expert management of breeding and maintenance of our mice as well as support by the Flow Cytometry facility and the Sequencing Facility. This work was funded by a Boehringer Ingelheim Fonds PhD Fellowship to M.V., a Wellcome Investigator Grant to B.S. and Cancer Research Programme Grant C4639/ A10822 to C.J.H. and C.R.W.

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    N2 - The aryl hydrocarbon receptor (AhR), a transcription factor known for mediating xenobiotic toxicity, is expressed in B cells, which are known targets for environmental pollutants. However, it is unclear what the physiological functions of AhR in B cells are. We show here that expression of Ahr in B cells is up-regulated upon B-cell receptor (BCR) engagement and IL-4 treatment. Addition of a natural ligand of AhR, FICZ, induces AhR translocation to the nucleus and transcription of the AhR target gene Cyp1a1, showing that the AhR pathway is functional in B cells. AhR-deficient (Ahr(-/-)) B cells proliferate less than AhR-sufficient (Ahr(+/+)) cells following in vitro BCR stimulation and in vivo adoptive transfer models confirmed that Ahr(-/-) B cells are outcompeted by Ahr(+/+) cells. Transcriptome comparison of AhR-deficient and AhR-sufficient B cells identified cyclin O (Ccno), a direct target of AhR, as a top candidate affected by AhR deficiency.

    AB - The aryl hydrocarbon receptor (AhR), a transcription factor known for mediating xenobiotic toxicity, is expressed in B cells, which are known targets for environmental pollutants. However, it is unclear what the physiological functions of AhR in B cells are. We show here that expression of Ahr in B cells is up-regulated upon B-cell receptor (BCR) engagement and IL-4 treatment. Addition of a natural ligand of AhR, FICZ, induces AhR translocation to the nucleus and transcription of the AhR target gene Cyp1a1, showing that the AhR pathway is functional in B cells. AhR-deficient (Ahr(-/-)) B cells proliferate less than AhR-sufficient (Ahr(+/+)) cells following in vitro BCR stimulation and in vivo adoptive transfer models confirmed that Ahr(-/-) B cells are outcompeted by Ahr(+/+) cells. Transcriptome comparison of AhR-deficient and AhR-sufficient B cells identified cyclin O (Ccno), a direct target of AhR, as a top candidate affected by AhR deficiency.

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