An inherently bifunctional subset of Foxp3+ T helper cells is controlled by the transcription factor eos

Immunity. 2013 May 23;38(5):998-1012. doi: 10.1016/j.immuni.2013.01.013. Epub 2013 May 16.


At sites of inflammation, certain regulatory T cells (Treg cells) can undergo rapid reprogramming into helper-like cells without loss of the transcription factor Foxp3. We show that reprogramming is controlled by downregulation of the transcription factor Eos (Ikzf4), an obligate corepressor for Foxp3. Reprogramming was restricted to a specific subset of "Eos-labile" Treg cells that was present in the thymus and identifiable by characteristic surface markers and DNA methylation. Mice made deficient in this subset became impaired in their ability to provide help for presentation of new antigens to naive T cells. Downregulation of Eos required the proinflammatory cytokine interleukin-6 (IL-6), and mice lacking IL-6 had impaired development and function of the Eos-labile subset. Conversely, the immunoregulatory enzyme IDO blocked loss of Eos and prevented the Eos-labile Treg cells from reprogramming. Thus, the Foxp3(+) lineage contains a committed subset of Treg cells capable of rapid conversion into biologically important helper cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / metabolism*
  • Cell Differentiation / immunology
  • DNA-Binding Proteins
  • Down-Regulation
  • Forkhead Transcription Factors / metabolism
  • Ikaros Transcription Factor / metabolism*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Lymphocyte Activation / immunology
  • Mice
  • Nerve Tissue Proteins / metabolism*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Thymus Gland


  • Carrier Proteins
  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interleukin-6
  • Nerve Tissue Proteins
  • Zfpn1a4 protein, mouse
  • Ikaros Transcription Factor

Associated data

  • GEO/GSE44380