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Fat-associated lymphoid clusters control local IgM secretion during pleural infection and lung inflammation

Author

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  • Lucy H. Jackson-Jones

    (Institute of Immunology and Infection Research, University of Edinburgh
    Centre for Cardiovascular Science, University of Edinburgh)

  • Sheelagh M. Duncan

    (Institute of Immunology and Infection Research, University of Edinburgh)

  • Marlène S. Magalhaes

    (Centre for Cardiovascular Science, University of Edinburgh)

  • Sharon M. Campbell

    (Institute of Immunology and Infection Research, University of Edinburgh)

  • Rick M. Maizels

    (Institute of Immunology and Infection Research, University of Edinburgh)

  • Henry J. McSorley

    (Institute of Immunology and Infection Research, University of Edinburgh
    Centre for Inflammation Research, University of Edinburgh)

  • Judith E. Allen

    (Institute of Immunology and Infection Research, University of Edinburgh
    Faculty of Biology, Medicine & Health, University of Manchester, AV Hill Building)

  • Cécile Bénézech

    (Centre for Cardiovascular Science, University of Edinburgh)

Abstract

Fat-associated lymphoid clusters (FALC) are inducible structures that support rapid innate-like B-cell immune responses in the serous cavities. Little is known about the physiological cues that activate FALCs in the pleural cavity and more generally the mechanisms controlling B-cell activation in FALCs. Here we show, using separate models of pleural nematode infection with Litomosoides sigmodontis and Altenaria alternata induced acute lung inflammation, that inflammation of the pleural cavity rapidly activates mediastinal and pericardial FALCs. IL-33 produced by FALC stroma is crucial for pleural B1-cell activation and local IgM secretion. However, B1 cells are not the direct target of IL-33, which instead requires IL-5 for activation. Moreover, lung inflammation leads to increased IL-5 production by type 2 cytokine-producing innate lymphoid cells (ILC2) in the FALC. These findings reveal a link between inflammation, IL-33 release by FALC stromal cells, ILC2 activation and pleural B-cell activation in FALCs, resulting in local and antigen-specific IgM production.

Suggested Citation

  • Lucy H. Jackson-Jones & Sheelagh M. Duncan & Marlène S. Magalhaes & Sharon M. Campbell & Rick M. Maizels & Henry J. McSorley & Judith E. Allen & Cécile Bénézech, 2016. "Fat-associated lymphoid clusters control local IgM secretion during pleural infection and lung inflammation," Nature Communications, Nature, vol. 7(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12651
    DOI: 10.1038/ncomms12651
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