title: Experimental priming of encephalitogenic Th1/Th17 cells requires pertussis toxin-driven IL-1β production by myeloid cells.
abstract: 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.
authors.affiliation: Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ronchi
authors.affiliation: Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
authors.forename: Camilla
authors.initials: C
authors.lastname: Basso
authors.affiliation: Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Preite
authors.affiliation: Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Reboldi
authors.affiliation: Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
authors.forename: Dirk
authors.identifier: 0000-0001-8385-8288
authors.initials: D
authors.lastname: Baumjohann
authors.affiliation: Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
authors.forename: Luana
authors.initials: L
authors.lastname: Perlini
authors.affiliation: Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.|Institute of Microbiology, D-BIOL, ETH Zurich, Vladimir-Prelog-Weg 4, CH-8093 Zurich, Switzerland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
authors.affiliation: Cellular Immunology Laboratory and Immune Regulation Laboratory, Institute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D037342:Pertussis Toxin / Q000276:immunology*; D053573:Receptors, Interleukin-1 Type I / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
chemical_list: D020381:Interleukin-17; D053573:Receptors, Interleukin-1 Type I; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D037342:Pertussis Toxin