The Transcription Factor MAZR/PATZ1 Regulates the Development of FOXP3+ Regulatory T Cells

Cell Rep. 2019 Dec 24;29(13):4447-4459.e6. doi: 10.1016/j.celrep.2019.11.089.

Abstract

Forkhead box protein P3+ (FOXP3+) regulatory T cells (Treg cells) play a key role in maintaining tolerance and immune homeostasis. Here, we report that a T cell-specific deletion of the transcription factor MAZR (also known as PATZ1) leads to an increased frequency of Treg cells, while enforced MAZR expression impairs Treg cell differentiation. Further, MAZR expression levels are progressively downregulated during thymic Treg cell development and during in-vitro-induced human Treg cell differentiation, suggesting that MAZR protein levels are critical for controlling Treg cell development. However, MAZR-deficient Treg cells show only minor transcriptional changes ex vivo, indicating that MAZR is not essential for establishing the transcriptional program of peripheral Treg cells. Finally, the loss of MAZR reduces the clinical score in dextran-sodium sulfate (DSS)-induced colitis, suggesting that MAZR activity in T cells controls the extent of intestinal inflammation. Together, these data indicate that MAZR is part of a Treg cell-intrinsic transcriptional network that modulates Treg cell development.

Keywords: DSS-induced colitis; FOXP3; MAZR; PATZ1; T(reg); regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Colitis / immunology
  • Dextran Sulfate
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Kruppel-Like Transcription Factors / metabolism*
  • Mice, Knockout
  • Neoplasm Proteins / metabolism*
  • Repressor Proteins / metabolism*
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / metabolism*
  • Thymus Gland / cytology
  • Transcription, Genetic

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Kruppel-Like Transcription Factors
  • Neoplasm Proteins
  • PATZ1 protein, human
  • Repressor Proteins
  • Zfp278 protein, mouse
  • Dextran Sulfate