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Transcriptional regulation of IL-9-producing CD4 T cells: use in cancer immunotherapy

Objective

Differentiation of naïve CD4 T cells in presence of TGF-beta and IL-4 has led to the identification of a novel IL-9-secreting-population of CD4 T cells, Th9 cells, which are characterized by their potent IL-9 release and their ability to induce proinflammatory responses in vivo. Co-transfer of in vitro differentiated Th9 cells from naïve T cells along with effector cells increase the severity of colitis in mice. Proinflammatory functions of Th9 cells have also been documented in the mouse model of human multiple sclerosis, Experimental Autoimmune Encephalomyelitis (EAE), in asthma and the existence of Th9 cells has been confirmed in humans. Nevertheless, while the transcription factors PU.1 and irf4 have been involved in Th9 cell development in mouse and humans, the mechanisms leading to the generation of these cells remain incompletely understood. In addition, the function of Th9 cells in cancer has never been explored. Our preliminary work suggests that the addition of a proinflammatory factor IL-1 beta during Th9 cell differentiation triggers the high expression of a transcription factor, which might cooperate with irf4 and PU.1 to dramatically enhance Th9 cell effector functions. Generation of Th9 cells in the presence of IL-1 beta also enhances the antitumor properties of Th9 cells in vivo. In this project, we aim to decipher the molecular mechanisms responsible for the effect of IL-1 beta on Th9 cells and identify the factors responsible for the anticancer efficacy of Th9 cells in vivo. Unraveling the mechanisms responsible for the enhanced anticancer efficacy of Th9 cells would not only provide a better characterization of Th9 cell development but would also urge scientists to contemplate their use in cancer immunotherapy.

Call for proposal

FP7-PEOPLE-2011-CIG
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Funding Scheme

MC-CIG - Support for training and career development of researcher (CIG)
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Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Address
Rue De Tolbiac 101
75654 Paris
France
Activity type
Research Organisations
EU contribution
€ 100 000
Administrative Contact
Sonia Robinet (Ms.)