Mouse Hobit is a homolog of the transcriptional repressor Blimp-1 that regulates NKT cell effector differentiation

Nat Immunol. 2012 Sep;13(9):864-71. doi: 10.1038/ni.2393. Epub 2012 Aug 12.

Abstract

The transcriptional repressor Blimp-1 mediates the terminal differentiation of many cell types, including T cells. Here we identified Hobit (Znf683) as a previously unrecognized homolog of Blimp-1 that was specifically expressed in mouse natural killer T cells (NKT cells). Through studies of Hobit-deficient mice, we found that Hobit was essential for the formation of mature thymic NKT cells. In the periphery, Hobit repressed the accumulation of interferon-γ (IFN-γ)-producing NK1.1(lo) NKT cells at steady state. After antigenic stimulation, Hobit repressed IFN-γ expression, whereas after innate stimulation, Hobit induced granzyme B expression. Thus, reminiscent of the function of Blimp-1 in other lymphocytes, Hobit controlled the maintenance of quiescent, fully differentiated NKT cells and regulated their immediate effector functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Differentiation / genetics*
  • Cell Differentiation / immunology
  • Flow Cytometry
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Natural Killer T-Cells / cytology*
  • Natural Killer T-Cells / immunology*
  • Phylogeny
  • Positive Regulatory Domain I-Binding Factor 1
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics

Substances

  • Prdm1 protein, mouse
  • Transcription Factors
  • Positive Regulatory Domain I-Binding Factor 1