Both IFN-γ and IL-17 are required for the development of severe autoimmune gastritis.
IL-17, produced by a distinct lineage of CD4(+)  helper T (Th) cells termed Th17 cells, induces the production of pro-inflammatory cytokines from resident cells and it has been demonstrated that over-expression of IL-17 plays a crucial role in the onset of several auto-immune diseases. Here we examined the role of IL-17 in the pathogenesis of autoimmune gastritis, a disease that was previously believed to be mediated by IFN-γ. Significantly higher levels of IL-17 and IFN-γ were found in the stomachs and stomach-draining lymph nodes of mice with severe autoimmune gastritis. Unlike IL-17, which was produced solely by CD4(+)  T cells in gastritic mice, the majority of IFN-γ-producing cells were CD8(+)  T cells. However, CD8(+)  T cells alone were not able to induce autoimmune gastritis. T cells that were deficient in IL-17 or IFN-γ production were able to induce autoimmune gastritis but to a much lower extent compared with the disease induced by wild-type T cells. These data demonstrate that production of neither IL-17 nor IFN-γ by effector T cells is essential for the initiation of autoimmune gastritis, but suggest that both are required for the disease to progress to the late pathogenic stage that includes significant tissue disruption.
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia.
Eric
E
Tu
Desmond K Y
DK
Ang
Shayne A
SA
Bellingham
Thea V
TV
Hogan
Michele W L
MW
Teng
Mark J
MJ
Smyth
Andrew F
AF
Hill
Ian R
IR
van Driel
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002478:Cells, Cultured; D018450:Disease Progression; D005756:Gastritis / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D058504:Th17 Cells / Q000276:immunology* / Q000637:transplantation
D020381:Interleukin-17; D007371:Interferon-gamma