Host dysbiosis negatively impacts IL-9-producing T-cell differentiation and antitumour immunity.
Br J Cancer
; 123(4): 534-541, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32499569
ABSTRACT
BACKGROUND:
Host-microbiota interactions shape T-cell differentiation and promote tumour immunity. Although IL-9-producing T cells have been described as potent antitumour effectors, their role in microbiota-mediated tumour control remains unclear.METHODS:
We analysed the impact of the intestinal microbiota on the differentiation of colonic lamina propria IL-9-producing T cells in germ-free and dysbiotic mice. Systemic effects of the intestinal microbiota on IL-9-producing T cells and the antitumour role of IL-9 were analysed in a model of melanoma-challenged dysbiotic mice.RESULTS:
We show that germ-free mice have lower frequency of colonic lamina propria IL-9-producing T cells when compared with conventional mice, and that intestinal microbiota reconstitution restores cell frequencies. Long-term antibiotic treatment promotes host dysbiosis, diminishes intestinal IL-4 and TGF-ß gene expression, decreases the frequency of colonic lamina propria IL-9-producing T cells, increases the susceptibility to tumour development and reduces the frequency of IL-9-producing T cells in the tumour microenvironment. Faecal transplant restores intestinal microbiota diversity, and the frequency of IL-9-producing T cells in the lungs of dysbiotic animals, restraining tumour burden. Finally, recombinant IL-9 injection enhances tumour control in dysbiotic mice.CONCLUSIONS:
Host-microbiota interactions are required for adequate differentiation and antitumour function of IL-9-producing T cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Interleucina-9
/
Disbiose
/
Vida Livre de Germes
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Melanoma
/
Antibacterianos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article