Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Frederick Masson1,2,
  2. Margherita Ghisi3,
  3. Joanna R. Groom1,2,
  4. Axel Kallies1,2,
  5. Cyril Seillet1,2,
  6. Ricky W. Johnstone3,4,
  7. Stephen L. Nutt1,2, and
  8. Gabrielle T. Belz1,2
  1. 1Division of Molecular Immunology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia;
  2. 2Department of Medical Biology, University of Melbourne, Melbourne, Australia;
  3. 3Peter MacCallum Cancer Centre, Melbourne, Australia; and
  4. 4Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia

Key Points

  • Loss of Id2 in T cells results in overexpression of IL-10 during influenza infection and GVHD and protects against GVHD immunopathology.

  • Id2 represses the direct E2A-mediated activation of the Il10 locus in effector T cells.


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.

  • Submitted March 7, 2014.
  • Accepted April 8, 2014.
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