Stat3 and Gfi-1 Transcription Factors Control Th17 Cell Immunosuppressive Activity via the Regulation of Ectonucleotidase Expression

6533b7d7fe1ef96bd126915a

RESEARCH PRODUCT

Stat3 and Gfi-1 Transcription Factors Control Th17 Cell Immunosuppressive Activity via the Regulation of Ectonucleotidase Expression

Bernhard Ryffel Simon C. Robson Sylvain Ladoire Jean René Pallandre François Ghiringhelli Lionel Apetoh Frédérique Végran Aziz Hichami Aziz Hichami Angélique Chevriaux Gérard Eberl Gérard Eberl Christophe Borg Julie Vincent Julie Vincent Cédric Rébé Grégoire Mignot David Masson David Masson Fanny Chalmin Valentin Derangère Mélanie Bruchard Mélanie Bruchard

subject

Adoptive cell transfer MESH : Transcription Factors Cellular differentiation MESH: Th17 Cells T-Lymphocytes Cell MESH : Promoter Regions Genetic MESH : RNA Small Interfering MESH: Mice Knockout Mice 0302 clinical medicine Transforming Growth Factor beta MESH: RNA Small Interfering MESH : STAT3 Transcription Factor Immunology and Allergy [ SDV.IMM ] Life Sciences [q-bio]/Immunology Ectonucleotidase MESH: Animals RNA Small Interfering STAT3 MESH: Lymphocytes Tumor-Infiltrating Promoter Regions Genetic MESH: Antigens CD 5'-Nucleotidase Regulation of gene expression Mice Knockout 0303 health sciences MESH : Gene Expression Regulation Apyrase MESH: STAT3 Transcription Factor MESH: Transcription Factors MESH: Gene Expression Regulation MESH : Mice Transgenic Cell biology MESH : Lymphocytes Tumor-Infiltrating DNA-Binding Proteins MESH : Apyrase Infectious Diseases medicine.anatomical_structure [SDV.IMM]Life Sciences [q-bio]/Immunology MESH : DNA-Binding Proteins MESH: Apyrase STAT3 Transcription Factor [SDV.IMM] Life Sciences [q-bio]/Immunology MESH : Interleukin-6 MESH: Mice Transgenic T cell Immunology Mice Transgenic MESH : Mice Inbred C57BL Biology 03 medical and health sciences Lymphocytes Tumor-Infiltrating MESH: Mice Inbred C57BL Antigens CD MESH: Promoter Regions Genetic MESH : 5'-Nucleotidase MESH : Mice medicine MESH : Antigens CD MESH : Th17 Cells Animals Transcription factor MESH: Mice MESH: Transforming Growth Factor beta 030304 developmental biology MESH : T-Lymphocytes Binding Sites Interleukin-6 MESH: Interleukin-6 Mice Inbred C57BL MESH: T-Lymphocytes MESH : Transforming Growth Factor beta MESH: Binding Sites Gene Expression Regulation biology.protein MESH : Mice Knockout Th17 Cells MESH : Animals MESH: 5'-Nucleotidase MESH: DNA-Binding Proteins MESH : Binding Sites 030215 immunology Transcription Factors

description

International audience; Although Th17 cells are known to promote tissue inflammation and autoimmunity, their role during cancer progression remains elusive. Here, we showed that in vitro Th17 cells generated with the cytokines IL-6 and TGF-β expressed CD39 and CD73 ectonucleotidases, leading to adenosine release and the subsequent suppression of CD4(+) and CD8(+) T cell effector functions. The IL-6-mediated activation of the transcription factor Stat3 and the TGF-β-driven downregulation of Gfi-1 transcription factor were both essential for the expression of ectonucleotidases during Th17 cell differentiation. Stat3 supported whereas Gfi-1 repressed CD39 and CD73 expression by binding to their promoters. Accordingly, Th17 cells differentiated with IL-1β, IL-6, and IL-23 but without TGF-β did not express ectonucleotidases and were not immunosuppressive. Finally, adoptive transfer of Th17 cells induced by TGF-β and IL-6 promoted tumor growth in a CD39-dependent manner. Thus, ectonucleotidase expression supports the immunosuppressive fate of Th17 cells in cancer.

year	journal	country	edition	language
2012-03-23	Immunity

10.1016/j.immuni.2011.12.019 http://dx.doi.org/10.1016/j.immuni.2011.12.019