The transcription factor Bhlhe40 is a switch of inflammatory versus antiinflammatory Th1 cell fate determination. Academic Article uri icon

Overview

abstract

  • Type 1 T helper (Th1) cells play a critical role in host defense against intracellular pathogens and in autoimmune diseases by producing a key inflammatory cytokine interferon (IFN)-γ; some Th1 cells can also be antiinflammatory through producing IL-10. However, the molecular switch for regulating the differentiation of inflammatory and antiinflammatory Th1 cells is still elusive. Here, we show that Bhlhe40-deficient CD4 Th1 cells produced less IFN-γ but substantially more IL-10 than wild-type Th1 cells both in vitro and in vivo. Bhlhe40-mediated IFN-γ production was independent of transcription factor T-bet regulation. Mice with conditional deletion of Bhlhe40 in T cells succumbed to Toxoplasma gondii infection, and blockade of IL-10 signaling during infection rescued these mice from death. Thus, our results demonstrate that transcription factor Bhlhe40 is a molecular switch for determining the fate of inflammatory and antiinflammatory Th1 cells.

authors

  • Yu, Fang
  • Sharma, Suveena
  • Jankovic, Dragana
  • Gurram, Rama Krishna
  • Su, Pan
  • Hu, Gangqing
  • Li, Rao
  • Rieder, Sadiye
  • Zhao, Keji
  • Sun, Bing
  • Zhu, Jinfang

publication date

  • May 17, 2018

Research

keywords

  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Lineage
  • Homeodomain Proteins
  • Inflammation
  • Th1 Cells

Identity

PubMed Central ID

  • PMC6028509

Scopus Document Identifier

  • 85052400624

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2012.09.007

PubMed ID

  • 29773643

Additional Document Info

volume

  • 215

issue

  • 7