Control of T helper 2 responses by transcription factor IRF4-dependent dendritic cells

Immunity. 2013 Oct 17;39(4):722-32. doi: 10.1016/j.immuni.2013.08.028. Epub 2013 Sep 26.

Abstract

CD4⁺ T cell differentiation is regulated by specialized antigen-presenting cells. Dendritic cells (DCs) produce cytokines that promote naive CD4⁺ T cell differentiation into T helper 1 (Th1), Th17, and inducible T regulatory (iTreg) cells. However, the initiation of Th2 cell responses remains poorly understood, although it is likely that more than one mechanism might be involved. Here we have defined a specific DC subset that is involved in Th2 cell differentiation in vivo in response to a protease allergen, as well as infection with Nippostrongylus brasiliensis. We have demonstrated that this subset is controlled by the transcription factor interferon regulatory factor 4 (IRF4), which is required for their differentiation and Th2 cell-inducing function. IRF4 is known to control Th2 cell differentiation and Th2 cell-associated suppressing function in Treg cells. Our finding suggests that IRF4 also plays a role in DCs where it controls the initiation of Th2 cell responses.

Publication types

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

MeSH terms

  • Allergens / immunology
  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / parasitology
  • Cell Differentiation
  • Coculture Techniques
  • Dendritic Cells / immunology*
  • Dendritic Cells / parasitology
  • Dendritic Cells / pathology
  • Gene Expression Regulation
  • Immunity, Cellular*
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / immunology*
  • Mice
  • Mice, Transgenic
  • Nippostrongylus / immunology
  • Ovalbumin / immunology
  • Signal Transduction
  • Strongylida Infections / immunology*
  • Strongylida Infections / parasitology
  • Strongylida Infections / pathology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / parasitology
  • T-Lymphocytes, Regulatory / pathology
  • Th1 Cells / immunology
  • Th1 Cells / parasitology
  • Th1 Cells / pathology
  • Th2 Cells / immunology*
  • Th2 Cells / parasitology
  • Th2 Cells / pathology

Substances

  • Allergens
  • Interferon Regulatory Factors
  • interferon regulatory factor-4
  • Ovalbumin