Batf is important for IL-4 expression in T follicular helper cells

Nat Commun. 2015 Aug 17:6:7997. doi: 10.1038/ncomms8997.

Abstract

Apart from T helper (Th)-2 cells, T follicular helper (Tfh) cells are a major class of IL-4-producing T cells, required for regulation of type 2 humoral immunity; however, transcriptional control of IL-4 production in Tfh cells remains mainly unknown. Here, we show that the basic leucine zipper transcription factor ATF-like, Batf is important for IL-4 expression in Tfh cells rather than in canonical Th2 cells. Functionally, Batf in cooperation with interferon regulatory factor (IRF) 4 along with Stat3 and Stat6 trigger IL-4 production in Tfh cells by directly binding to and activation of the CNS2 region in the IL-4 locus. In addition, Batf-to-c-Maf signalling is an important determinant of IL-4 expression in Tfh cells. Batf deficiency impairs the generation of IL-4-producing Tfh cells that results in protection against allergic asthma. Our results thus indicate a positive role of Batf in promoting the generation of pro-allergic IL-4-producing Tfh cells.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • Asthma / immunology
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • Bone Marrow Cells
  • Cell Differentiation
  • Chromatin Immunoprecipitation
  • Gene Expression Regulation / physiology*
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Ovalbumin / immunology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • T-Lymphocytes, Helper-Inducer / physiology*

Substances

  • Basic-Leucine Zipper Transcription Factors
  • Batf protein, mouse
  • RNA, Messenger
  • Receptors, Antigen, T-Cell, alpha-beta
  • Interleukin-4
  • Ovalbumin