Id2 and Id3 maintain the regulatory T cell pool to suppress inflammatory disease

Nat Immunol. 2014 Aug;15(8):767-76. doi: 10.1038/ni.2928. Epub 2014 Jun 29.


Regulatory T (Treg) cells suppress the development of inflammatory disease, but our knowledge of transcriptional regulators that control this function remains incomplete. Here we show that expression of Id2 and Id3 in Treg cells was required to suppress development of fatal inflammatory disease. We found that T cell antigen receptor (TCR)-driven signaling initially decreased the abundance of Id3, which led to the activation of a follicular regulatory T (TFR) cell-specific transcription signature. However, sustained lower abundance of Id2 and Id3 interfered with proper development of TFR cells. Depletion of Id2 and Id3 expression in Treg cells resulted in compromised maintenance and localization of the Treg cell population. Thus, Id2 and Id3 enforce TFR cell checkpoints and control the maintenance and homing of Treg cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology
  • Cell Movement / immunology
  • Cell Proliferation
  • Female
  • Forkhead Transcription Factors / biosynthesis
  • Gene Expression Regulation / immunology
  • Green Fluorescent Proteins / genetics
  • Inflammation / genetics
  • Inflammation / immunology*
  • Inhibitor of Differentiation Protein 2 / biosynthesis
  • Inhibitor of Differentiation Protein 2 / genetics
  • Inhibitor of Differentiation Protein 2 / immunology*
  • Inhibitor of Differentiation Proteins / biosynthesis
  • Inhibitor of Differentiation Proteins / genetics
  • Inhibitor of Differentiation Proteins / immunology*
  • Interleukin-10 / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, CXCR5 / biosynthesis
  • Sequence Analysis, RNA
  • T-Lymphocytes, Regulatory / immunology*


  • CXCR5 protein, mouse
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • IL10 protein, mouse
  • Idb2 protein, mouse
  • Inhibitor of Differentiation Protein 2
  • Inhibitor of Differentiation Proteins
  • Receptors, Antigen, T-Cell
  • Receptors, CXCR5
  • Interleukin-10
  • Idb3 protein, mouse
  • Green Fluorescent Proteins

Associated data

  • GEO/GSE57682