Host dysbiosis negatively impacts IL-9-producing T-cell differentiation and antitumour immunity
Open Access
- 5 June 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in British Journal of Cancer
- Vol. 123 (4), 534-541
- https://doi.org/10.1038/s41416-020-0915-6
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-β 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.Keywords
Funding Information
- Fundação de Amparo à Pesquisa do Estado de São Paulo
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