The transcription factors Thpok and LRF are necessary and partly redundant for T helper cell differentiation

Immunity. 2012 Oct 19;37(4):622-33. doi: 10.1016/j.immuni.2012.06.019. Epub 2012 Oct 4.


T helper (Th) cells are critical for defenses against infection and recognize peptides bound to class II major histocompatibility complex (MHC II) molecules. Although transcription factors have been identified that direct Th cells into specific effector fates, whether a "master" regulator controls the developmental program common to all Th cells remains unclear. Here, we showed that the two transcription factors Thpok and LRF share this function. Although disruption of both factors did not prevent the generation of MHC II-specific T cells, these cells failed to express Th cell genes or undergo Th cell differentiation in vivo. In contrast, T cells lacking Thpok, which only displayed LRF-dependent functions, contributed to multiple effector responses, both in vitro and in vivo, with the notable exception of Th2 cell responses that control extracellular parasites. These findings identify the Thpok-LRF pair as a core node of Th cell differentiation and function.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cells, Cultured
  • DNA-Binding Proteins / immunology*
  • Gene Expression Regulation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Transcription Factors / deficiency
  • Transcription Factors / immunology*


  • DNA-Binding Proteins
  • Th-POK protein, mouse
  • Transcription Factors
  • Zbtb7a protein, mouse