Experimental priming of encephalitogenic Th1/Th17 cells requires pertussis toxin-driven IL-1β production by myeloid cells
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Ronchi, Francesca
Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Basso, Camilla
Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Preite, Silvia
Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Reboldi, Andrea
Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Baumjohann, Dirk
Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Perlini, Luana
Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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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
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Sallusto, Federica
Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Published in:
- Nature communications. - 2016, vol. 7, p. 11541
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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Biology, life sciences
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License undefined
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https://n2t.net/ark:/12658/srd1318864
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