•  The mice exhibit more severe lesions that were associated with the appearance of the IL-17+ CD4+ cells. •  IL-27 administration prevents the development of abnormal Th17 cells during Leishmaniasis. •  The mice display a low percentage of IL-10+ IFN-γ− CD4+ cells and more severe lesions at week 6 post-infection. The gene discussed is IL10; the disease is leishmaniasis.