Transcription factor IRF8 controls Th1-like regulatory T-cell function

Cell Mol Immunol. 2016 Nov;13(6):785-794. doi: 10.1038/cmi.2015.72. Epub 2015 Jul 13.

Abstract

Recent studies have suggested that regulatory T (Treg) cells comprise a heterogeneous population that regulates various aspects of the immune response, and that Treg cells use the factors that are expressed in their target cells to regulate them. We searched for factors that regulate Th1 response in Treg cells using a meta-analysis. In the process, we discovered that transcription factor interferon regulatory factor 8 (IRF8) was selectively expressed in Treg and Th1 cells. IRF8-deficient Treg cells showed defective expression of CXCR3 and aberrant expression of the Il4 and Il17 genes. Upon treatment with alpha galactosyl-C18-ceramide (αGal-C18-Cer), IRF8-deficient mice showed defective Treg cell recruitment in the liver. Eliciting Th1 immune response by anti-CD40 antibody injection in mice induced IRF8 expression in Treg cells. The expression of IRF8 was induced by Foxp3 in Treg cells. IRF8 had no effect on T-bet expression in Treg and vice versa. Thus, our results strongly suggest that IRF8 controls Th1 immune response in Treg cells independent of T-bet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ceramides
  • Disease Models, Animal
  • Forkhead Transcription Factors / metabolism
  • Hepatitis / immunology
  • Hepatitis / pathology
  • Immunity, Cellular
  • Inflammation / immunology
  • Inflammation / pathology
  • Interferon Regulatory Factors / deficiency
  • Interferon Regulatory Factors / metabolism*
  • Interleukin-17 / metabolism
  • Interleukin-4 / metabolism
  • Mice, Inbred C57BL
  • Receptors, CXCR3 / metabolism
  • T-Box Domain Proteins / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-bet Transcription Factor
  • Th1 Cells / immunology*
  • Up-Regulation

Substances

  • Ceramides
  • Cxcr3 protein, mouse
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interferon Regulatory Factors
  • Interleukin-17
  • Receptors, CXCR3
  • T-Box Domain Proteins
  • T-bet Transcription Factor
  • interferon regulatory factor-8
  • Interleukin-4