Experimental priming of encephalitogenic Th1/Th17 cells requires pertussis toxin-driven IL-1β production by myeloid cells

Ronchi, Francesca; Basso, Camilla; Preite, Silvia; Reboldi, Andrea; Baumjohann, Dirk; Perlini, Luana; Lanzavecchia, Antonio; Sallusto, Federica

doi:10.1038/ncomms11541

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Journal article

Experimental priming of encephalitogenic Th1/Th17 cells requires pertussis toxin-driven IL-1β production by myeloid cells

Ronchi, Francesca Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Basso, Camilla Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Preite, Silvia Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Reboldi, Andrea Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Baumjohann, Dirk Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Perlini, Luana Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Lanzavecchia, Antonio Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Institute of Microbiology, D-BIOL, ETH Zurich, Vladimir-Prelog-Weg 4, CH-8093 Zurich, Switzerland
Sallusto, Federica Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland

18.05.2016

Published in:

Nature communications. - 2016, vol. 7, p. 11541

Cell death and immune response

English CD4+ Th17 are heterogeneous in terms of cytokine production and capacity to initiate autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE). Here we demonstrate that experimental priming of encephalitogenic Th cells expressing RORγt and T-bet and producing IL-17A, IFN-γ and GM-CSF but not IL-10 (Th1/Th17), is dependent on the presence of pertussis toxin (PTX) at the time of immunization. PTX induces early production of IL-1β by CD11b+CCR2+Gr1+ myeloid cells, which are rapidly recruited to antigen-draining lymph nodes. PTX-induced generation of Th1/Th17 cells is impaired in IL-1β- and ASC-deficient mice and in mice in which myeloid cells are depleted or fail to migrate to lymph nodes and requires expression of IL-1R1 and MyD88 on both T cells and non-T cells. Collectively, these data shed light on the enigmatic function of PTX in EAE induction and suggest that inflammatory monocytes and microbial infection can influence differentiation of pathogenic Th1/Th17 cells in autoimmune diseases through production of IL-1β.

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