Author:
Almeida Rafael Ribeiro,Vieira Raquel de Souza,Castoldi Angela,Terra Fernanda Fernandes,Melo Amanda Campelo L.,Canesso Maria Cecília Campos,Lemos Luísa,Cipelli Marcella,Rana Nisha,Hiyane Meire Ioshie,Pearce Erika L.,Martins Flaviano dos Santos,Faria Ana Maria Caetano de,Câmara Niels Olsen Saraiva
Abstract
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.
Funder
Fundação de Amparo à Pesquisa do Estado de São Paulo
Publisher
Springer Science and Business Media LLC
Cited by
14 articles.
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