Ronchi, Francesca Basso, Camilla Preite, Silvia Reboldi, Andrea Baumjohann, Dirk Perlini, Luana Lanzavecchia, Antonio Sallusto, Federica 2016-05-18 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. application/pdf https://susi.usi.ch/global/documents/318864 https://n2t.net/ark:/12658/srd1318864 https://susi.usi.ch/documents/318864/files/Ronchi_NC_2016.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1038/ncomms11541 info:eu-repo/semantics/altIdentifier/ark/12658/srd1318864 info:eu-repo/semantics/openAccess CC BY Nature communications. - 2016, vol. 7, p. 11541 Autoimmune diseases Cell death and immune response Cell signalling T-helper 17 cells info:eu-repo/classification/udc/57/59 Experimental priming of encephalitogenic Th1/Th17 cells requires pertussis toxin-driven IL-1β production by myeloid cells http://purl.org/coar/resource_type/c_6501