Mutual expression of the transcription factors Runx3 and ThPOK regulates intestinal CD4⁺ T cell immunity

Nat Immunol. 2013 Mar;14(3):271-80. doi: 10.1038/ni.2518. Epub 2013 Jan 20.


The gut mucosa hosts large numbers of activated lymphocytes that are exposed to stimuli from the diet, microbiota and pathogens. Although CD4(+) T cells are crucial for defense, intestinal homeostasis precludes exaggerated responses to luminal contents, whether they are harmful or not. We investigated mechanisms used by CD4(+) T cells to avoid excessive activation in the intestine. Using genetic tools to label and interfere with T cell-development transcription factors, we found that CD4(+) T cells acquired the CD8-lineage transcription factor Runx3 and lost the CD4-lineage transcription factor ThPOK and their differentiation into the T(H)17 subset of helper T cells and colitogenic potential, in a manner dependent on transforming growth factor-β (TGF-β) and retinoic acid. Our results demonstrate considerable plasticity in the CD4(+) T cell lineage that allows chronic exposure to luminal antigens without pathological inflammation.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD8 Antigens / immunology
  • Cell Differentiation
  • Cells, Cultured
  • Citrobacter rodentium / immunology
  • Colitis
  • Core Binding Factor Alpha 3 Subunit / metabolism*
  • Enterobacteriaceae Infections / immunology
  • Homeodomain Proteins / genetics
  • Inflammation / immunology
  • Intestinal Mucosa / immunology*
  • Intestines / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Signal Transduction
  • Tamoxifen / pharmacology
  • Transcription Factors / metabolism*
  • Transforming Growth Factor beta / metabolism
  • Tretinoin / metabolism


  • CD8 Antigens
  • Core Binding Factor Alpha 3 Subunit
  • Homeodomain Proteins
  • Runx3 protein, mouse
  • Th-POK protein, mouse
  • Transcription Factors
  • Transforming Growth Factor beta
  • Tamoxifen
  • RAG-1 protein
  • Tretinoin