title: The pathogenic Th17 cell response to major schistosome egg antigen is sequentially dependent on IL-23 and IL-1β.
abstract: CBA/J mice infected with the helminth Schistosoma mansoni develop severe CD4 T cell-mediated hepatic granulomatous inflammation against parasite eggs associated with a robust Th17 cell response. We investigated the requisites for Th17 cell development using novel CD4 T cells expressing a transgenic TCR specific for the major Sm-p40 egg Ag, which produce IL-17 when stimulated with live schistosome eggs. Neutralization of IL-23 or blockade of the IL-1 receptor, but not IL-6 neutralization, abrogated egg-induced IL-17 secretion by transgenic T cells, whereas exogenous IL-23 or IL-1β reconstituted their ability to produce IL-17 when stimulated by syngeneic IL-12p40-deficient dendritic cells. Kinetic analysis demonstrated that IL-17 production was initiated by IL-23 and amplified by IL-1β. Significantly, schistosome-infected IL-12p40-deficient or IL-1R antagonist-treated CBA/J mice developed markedly reduced hepatic immunopathology with a dampened egg Ag-specific IL-17 response. These results demonstrate that the IL-23-IL-1-IL-17 axis has a central role in the development of severe schistosome egg-induced immunopathology.
authors: Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors: Mara G
authors: MG
authors: Shainheit
authors: Krzysztof W
authors: KW
authors: Lasocki
authors: Eduardo
authors: E
authors: Finger
authors: Bridget M
authors: BM
authors: Larkin
authors: Patrick M
authors: PM
authors: Smith
authors: Arlene H
authors: AH
authors: Sharpe
authors: Charles A
authors: CA
authors: Dinarello
authors: Laura I
authors: LI
authors: Rutitzky
authors: Miguel J
authors: MJ
authors: Stadecker
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000502:physiology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015801:Helminth Proteins / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000502:physiology*; D053759:Interleukin-23 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D058504:Th17 Cells / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology
chemical_list: D000947:Antigens, Helminth; D018984:Epitopes, T-Lymphocyte; D015801:Helminth Proteins; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; C055560:p40 egg antigen, Schistosoma; D007371:Interferon-gamma