Role of Blimp-1 in differentiation and function of Th9 cells.
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Full text | |
Author(s): Show less - |
Almeida, Rafael Ribeiro
[1, 2]
;
Vieira, Raquel de Souza
[1, 2]
;
Castoldi, Angela
[1]
;
Terra, Fernanda Fernandes
[1]
;
Melo, Amanda Campelo L.
[1]
;
Campos Canesso, Maria Cecilia
[3]
;
Lemos, Luisa
[3]
;
Cipelli, Marcella
[1]
;
Rana, Nisha
[4]
;
Hiyane, Meire Ioshie
[1]
;
Pearce, Erika L.
[4]
;
Martins, Flaviano dos Santos
[5]
;
Caetano de Faria, Ana Maria
[3]
;
Saraiva Camara, Niels Olsen
[1]
Total Authors: 14
|
Affiliation: | [1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo - Brazil
[2] Univ Sao Paulo, Heart Inst INCOR, Lab Immunol, Sao Paulo - Brazil
[3] Univ Fed Minas Gerais, Biol Sci Inst, Dept Biochem & Immunol, Belo Horizonte, MG - Brazil
[4] Max Planck Inst Epigenet & Immunobiol, Dept Immunometab, Freiburg - Germany
[5] Univ Fed Minas Gerais, Biol Sci Inst, Dept Microbiol, Belo Horizonte, MG - Brazil
Total Affiliations: 5
|
Document type: | Journal article |
Source: | BRITISH JOURNAL OF CANCER; v. 123, n. 4 JUN 2020. |
Web of Science Citations: | 2 |
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-beta 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. (AU) | |
FAPESP's process: | 15/13817-0 - The role of microbiota in the development of Th9 cells-mediated antitumor activity |
Grantee: | Rafael Ribeiro Almeida |
Support Opportunities: | Scholarships in Brazil - Post-Doctoral |