Both IFN-[gamma] and IL-17 are required for the development of severe autoimmune gastritis

• Published in: European journal of immunology 2012-10, Vol.42 (10), p.2574-2583
• Main Authors: Tu, Eric, Ang, Desmond KY, Bellingham, Shayne A, Hogan, Thea V, Teng, Michele W L, Smyth, Mark J, Hill, Andrew F, van Driel, Ian R
• Format: Article
• Language: English
• Subjects: Autoimmune diseases; Disease; Immune system; Lymphocytes
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201142341

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-[gamma]. Significantly higher levels of IL-17 and IFN-[gamma] 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-[gamma]-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-[gamma] 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-[gamma] 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. [PUBLICATION ABSTRACT]