The transcription factor IRF1 dictates the IL-21-dependent anticancer functions of TH9 cells

Frédérique Végran; Hélène Berger; Romain Boidot; Grégoire Mignot; Mélanie Bruchard; Magalie Dosset; Fanny Chalmin; Cédric Rébé; Valentin Dérangère; Bernhard Ryffel; Masashi Kato; Armelle Prévost-Blondel; François Ghiringhelli; Lionel Apetoh

doi:10.1038/ni.2925

The transcription factor IRF1 dictates the IL-21-dependent anticancer functions of TH9 cells

Nat Immunol. 2014 Aug;15(8):758-66. doi: 10.1038/ni.2925. Epub 2014 Jun 29.

Affiliations

¹ 1] INSERM, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France. [3].
² Centre Georges François Leclerc, Dijon, France.
³ 1] INSERM, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France.
⁴ 1] INSERM, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France. [3] Centre Georges François Leclerc, Dijon, France.
⁵ 1] CNRS and University, UMR7355, Orléans, France. [2] Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
⁶ Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Aichi, Japan.
⁷ 1] CNRS, UMR 8104, Paris, France. [2] INSERM, U1016, Paris, France. [3] Paris Descartes University, Cochin Institute, Paris, France.
⁸ 1] INSERM, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France. [3] Centre Georges François Leclerc, Dijon, France. [4].

PMID: 24973819
DOI: 10.1038/ni.2925

Abstract

The TH9 subset of helper T cells was initially shown to contribute to the induction of autoimmune and allergic diseases, but subsequent evidence has suggested that these cells also exert antitumor activities. However, the molecular events that account for their effector properties are elusive. Here we found that the transcription factor IRF1 enhanced the effector function of TH9 cells and dictated their anticancer properties. Under TH9-skewing conditions, interleukin 1β (IL-1β) induced phosphorylation of the transcription factor STAT1 and subsequent expression of IRF1, which bound to the promoters of Il9 and Il21 and enhanced secretion of the cytokines IL-9 and IL-21 from TH9 cells. Furthermore, IL-1β-induced TH9 cells exerted potent anticancer functions in an IRF1- and IL-21-dependent manner. Our findings thus identify IRF1 as a target for controlling the function of TH9 cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3 Cells
Animals
Base Sequence
Cell Line
Female
Green Fluorescent Proteins / biosynthesis
Green Fluorescent Proteins / genetics
Interferon Regulatory Factor-1 / biosynthesis
Interferon Regulatory Factor-1 / immunology*
Interferon-gamma / genetics
Interferon-gamma / immunology
Interleukin-10 / antagonists & inhibitors
Interleukin-10 / immunology
Interleukin-9 / genetics
Interleukin-9 / immunology
Interleukin-9 / metabolism
Interleukins / genetics
Interleukins / immunology*
Interleukins / metabolism
Melanoma, Experimental / immunology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Ovalbumin / immunology
Phosphorylation / immunology
Proto-Oncogene Proteins c-fyn / antagonists & inhibitors
Proto-Oncogene Proteins c-fyn / genetics
RNA Interference
RNA, Small Interfering
STAT1 Transcription Factor / immunology
Sequence Analysis, RNA
T-Lymphocytes, Helper-Inducer / immunology*
T-Lymphocytes, Helper-Inducer / metabolism

Substances

IL10 protein, mouse
Interferon Regulatory Factor-1
Interleukin-9
Interleukins
Irf1 protein, mouse
RNA, Small Interfering
STAT1 Transcription Factor
Stat1 protein, mouse
Interleukin-10
Green Fluorescent Proteins
Interferon-gamma
Ovalbumin
Fyn protein, mouse
Proto-Oncogene Proteins c-fyn
interleukin-21

Associated data

GEO/GSE54697