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 PMID:25343476  

Zinc finger protein Zfp335 is required for the formation of the naïve T cell compartment.

Brenda Y Han | Shuang Wu | Chuan-Sheng Foo | Robert M Horton | Craig N Jenne | Susan R Watson | Belinda Whittle | Chris C Goodnow | Jason G Cyster
eLife | 2014

The generation of naïve T lymphocytes is critical for immune function yet the mechanisms governing their maturation remain incompletely understood. We have identified a mouse mutant, bloto, that harbors a hypomorphic mutation in the zinc finger protein Zfp335. Zfp335(bloto/bloto) mice exhibit a naïve T cell deficiency due to an intrinsic developmental defect that begins to manifest in the thymus and continues into the periphery, affecting T cells that have recently undergone thymic egress. The effects of Zfp335(bloto) are multigenic and cannot be attributed to altered thymic selection, proliferation or Bcl2-dependent survival. Zfp335 binds to promoter regions via a consensus motif, and its target genes are enriched in categories related to protein metabolism, mitochondrial function, and transcriptional regulation. Restoring the expression of one target, Ankle2, partially rescues T cell maturation. These findings identify Zfp335 as a transcription factor and essential regulator of late-stage intrathymic and post-thymic T cell maturation.

Pubmed ID: 25343476

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: HHSN272201300006C
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI052127
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI074847
  • Agency: NIAID NIH HHS, United States
    Id: U19 AI100627

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