Id2 represses E2A-mediated activation of IL-10 expression in T cells

Frederick Masson; Margherita Ghisi; Joanna R Groom; Axel Kallies; Cyril Seillet; Ricky W Johnstone; Stephen L Nutt; Gabrielle T Belz

doi:10.1182/blood-2014-03-561456

Id2 represses E2A-mediated activation of IL-10 expression in T cells

Blood. 2014 May 29;123(22):3420-8. doi: 10.1182/blood-2014-03-561456. Epub 2014 Apr 10.

Authors

Frederick Masson¹, Margherita Ghisi², Joanna R Groom¹, Axel Kallies¹, Cyril Seillet¹, Ricky W Johnstone³, Stephen L Nutt¹, Gabrielle T Belz¹

Affiliations

¹ Division of Molecular Immunology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia;
² Peter MacCallum Cancer Centre, Melbourne, Australia; and.
³ Peter MacCallum Cancer Centre, Melbourne, Australia; and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.

PMID: 24723679
DOI: 10.1182/blood-2014-03-561456

Abstract

Interleukin-10 (IL-10) is a key immunoregulatory cytokine that functions to prevent inflammatory and autoimmune diseases. Despite the critical role for IL-10 produced by effector CD8(+) T cells during pathogen infection and autoimmunity, the mechanisms regulating its production are poorly understood. We show that loss of the inhibitor of DNA binding 2 (Id2) in T cells resulted in aberrant IL-10 expression in vitro and in vivo during influenza virus infection and in a model of acute graft-versus-host disease (GVHD). Furthermore, IL-10 overproduction substantially reduced the immunopathology associated with GVHD. We demonstrate that Id2 acts to repress the E2A-mediated trans-activation of the Il10 locus. Collectively, our findings uncover a key regulatory role of Id2 during effector T cell differentiation necessary to limit IL-10 production by activated T cells and minimize their suppressive activity during the effector phase of disease control.

Publication types

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

MeSH terms

Animals
Basic Helix-Loop-Helix Transcription Factors / metabolism*
Bone Marrow / pathology
CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / metabolism
Disease Models, Animal
Epigenesis, Genetic
Gene Expression Regulation
Genetic Loci
Graft vs Host Disease / genetics
Graft vs Host Disease / immunology
Graft vs Host Disease / metabolism
Graft vs Host Disease / mortality
Inhibitor of Differentiation Protein 2 / deficiency
Inhibitor of Differentiation Protein 2 / genetics
Inhibitor of Differentiation Protein 2 / metabolism*
Interleukin-10 / genetics*
Interleukin-10 / metabolism
Mice
Mice, Knockout
Orthomyxoviridae Infections / genetics
Orthomyxoviridae Infections / immunology
Orthomyxoviridae Infections / metabolism
Orthomyxoviridae Infections / mortality
T-Lymphocyte Subsets / metabolism*
Transcriptional Activation*

Substances

Basic Helix-Loop-Helix Transcription Factors
Inhibitor of Differentiation Protein 2
Tcf3 protein, mouse
Interleukin-10