Logo Logo
Help
Contact
Switch Language to German
Ronchi, Francesca; Basso, Camilla; Preite, Silvia; Reboldi, Andrea; Baumjohann, Dirk; Perlini, Luana; Lanzavecchia, Antonio; Sallusto, Federica (2016): Experimental priming of encephalitogenic Th1/Th17 cells requires pertussis toxin-driven IL-1 beta production by myeloid cells. In: Nature Communications, Vol. 7, 11541
[img]
Preview
707kB

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 ROR gamma t and T-bet and producing IL-17A, IFN-gamma 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-1 beta 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-1 beta- 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-1 beta.