Klf4 expression in conventional dendritic cells is required for T helper 2 cell responses

Immunity. 2015 May 19;42(5):916-28. doi: 10.1016/j.immuni.2015.04.017.

Abstract

The two major lineages of classical dendritic cells (cDCs) express and require either IRF8 or IRF4 transcription factors for their development and function. IRF8-dependent cDCs promote anti-viral and T-helper 1 (Th1) cell responses, whereas IRF4-expressing cDCs have been implicated in controlling both Th2 and Th17 cell responses. Here, we have provided evidence that Kruppel-like factor 4 (Klf4) is required in IRF4-expressing cDCs to promote Th2, but not Th17, cell responses in vivo. Conditional Klf4 deletion within cDCs impaired Th2 cell responses during Schistosoma mansoni infection, Schistosoma egg antigen (SEA) immunization, and house dust mite (HDM) challenge without affecting cytotoxic T lymphocyte (CTL), Th1 cell, or Th17 cell responses to herpes simplex virus, Toxoplasma gondii, and Citrobacter rodentium infections. Further, Klf4 deletion reduced IRF4 expression in pre-cDCs and resulted in selective loss of IRF4-expressing cDCs subsets in several tissues. These results indicate that Klf4 guides a transcriptional program promoting IRF4-expressing cDCs heterogeneity.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Helminth / immunology
  • Asthma / immunology
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Enterobacteriaceae Infections / immunology
  • Gene Deletion
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Herpes Simplex / immunology
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / immunology
  • Kruppel-Like Transcription Factors / genetics*
  • Kruppel-Like Transcription Factors / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Pyroglyphidae
  • Schistosomiasis mansoni / immunology*
  • Th2 Cells / cytology
  • Th2 Cells / immunology*
  • Toxoplasmosis / immunology

Substances

  • Antigens, Helminth
  • GKLF protein
  • Interferon Regulatory Factors
  • Kruppel-Like Transcription Factors
  • interferon regulatory factor-4

Associated data

  • GEO/GSE68590