Programmed death one homolog maintains the pool size of regulatory T cells by promoting their differentiation and stability

Sci Rep. 2017 Jul 20;7(1):6086. doi: 10.1038/s41598-017-06410-w.

Abstract

Programmed death one homolog (PD-1H) is an immunoglobulin superfamily molecule and primarily acts as a coinhibitor in the initiation of T cell response to antigens. Here, we report that genetic ablation of PD-1H in mice blocks the differentiation of naive T cells to Foxp3+ inducible Treg cells (iTreg) with a significant decrease of iTreg in lymphoid organs. This effect of PD-1H is highly specific for iTreg because both naturally generated iTreg in gut-related tissues and in vitro induced iTreg by TGF-β were decreased whereas the genesis of natural Treg (nTreg) remains normal. The suppressive function of both iTreg and nTreg, however, is not affected by the loss of PD-1H. In addition to decreased production, PD-1H deficient iTreg could also rapidly convert to CD4+ T helper 1 or T helper 17 cells in an inflammatory environment. Our results indicate that PD-1H is required for maintenance of iTreg pool size by promoting its differentiation and preventing its conversion to other CD4+ T cell subsets. These findings may have important implications for manipulating Tregs to control inflammation.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Biomarkers
  • Cell Differentiation / genetics*
  • Cytokines / metabolism
  • Enhancer Elements, Genetic
  • Forkhead Transcription Factors / genetics
  • Immune Tolerance
  • Inflammation Mediators / metabolism
  • Membrane Proteins / genetics*
  • Methylation
  • Mice
  • Mice, Knockout
  • STAT3 Transcription Factor / metabolism
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • Th17 Cells / cytology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism

Substances

  • Biomarkers
  • Cytokines
  • Dies1 protein, mouse
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Inflammation Mediators
  • Membrane Proteins
  • STAT3 Transcription Factor