A carregar...
Publicação
T cell polarization influences the development of IBD-associated neoplasia
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 1.71 MB | Adobe PDF |
Autores
Orientador(es)
Resumo(s)
Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammation of the gastrointestinal tract. It is an example of the widespread concept that chronic inflammation is a cancer risk factor since patients have an increased risk of colorectal cancer. Classically, this association has been explained by the establishment of an inflammatory environment that favors cell proliferation, angiogenesis and, ultimately, neoplastic risk. We hypothesize that, besides inflammation itself, the polarization of T helper (Th) cells towards branches that are pro- or anti-tumourigenic is an important cancer risk factor in chronic inflammation, namely IBD, and that Th1 cells are anti while Th17 cells are pro-tumourigenic in this setting.
To recapitulate tumour development in the context of chronic inflammation we used the azoxymethane and dextran sulphate sodium (AOM+DSS) chemical carcinogenesis mouse model. Cytokines produced by each of the cell subsets - IFN-γ for Th1 cells or IL-17F for Th17 cells - were administered to AOM+DSS treated C57BL/6 mice to polarize inflammation into the two different types of response. Mice were euthanized after two (early-endpoint experiment) or three (late-endpoint) DSS cycles. Tumour number and area were quantified macroscopically and tissue was collected for histological analysis and for immunohistochemistry with the lymphocytic lineage markers CD4, CD8 and Rorγt.
Macroscopically, IL-17F treated mice had more lesions than IFN-γ treated mice in both experiments, though only statistically significantly in the late-endpoint experiment. Histologically, IFN-γ treated mice in the late-endpoint experiment had fewer neoplastic lesions than the control group and the IL-17F group, although not significantly. No major differences were observed in the tumour CD4+, CD8+ and Rorγt+ cell densities between the groups for both experiments.
The cytokine treatment influenced malignancy development: mice treated with IFN-γ, which mimics a Th1 cell response, developed less neoplastic lesions than mice treated with IL-17F, which mimics a Th17 cell response.
Descrição
Palavras-chave
Inflammatory bowel disease Th1 Th17 AOM DSS colorectal cancer