Th9 cell development requires a BATF-regulated transcriptional network

J Clin Invest. 2013 Nov;123(11):4641-53. doi: 10.1172/JCI69489.


T helper 9 (Th9) cells are specialized for the production of IL-9, promote allergic inflammation in mice, and are associated with allergic disease in humans. It has not been determined whether Th9 cells express a characteristic transcriptional signature. In this study, we performed microarray analysis to identify genes enriched in Th9 cells compared with other Th subsets. This analysis defined a transcriptional regulatory network required for the expression of a subset of Th9-enriched genes. The activator protein 1 (AP1) family transcription factor BATF (B cell, activating transcription factor–like) was among the genes enriched in Th9 cells and was required for the expression of IL-9 and other Th9-associated genes in both human and mouse T cells. The expression of BATF was increased in Th9 cultures derived from atopic infants compared with Th9 cultures from control infants. T cells deficient in BATF expression had a diminished capacity to promote allergic inflammation compared with wild-type controls. Moreover, mouse Th9 cells ectopically expressing BATF were more efficient at promoting allergic inflammation than control transduced cells. These data indicate that BATF is a central regulator of the Th9 phenotype and contributes to the development of allergic inflammation.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • Basic-Leucine Zipper Transcription Factors / deficiency
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • Cell Lineage / genetics
  • Cell Lineage / immunology
  • Humans
  • Hypersensitivity / etiology
  • Hypersensitivity / immunology
  • Hypersensitivity / metabolism
  • Hypersensitivity, Immediate / genetics
  • Hypersensitivity, Immediate / immunology
  • Hypersensitivity, Immediate / metabolism
  • Infant
  • Inflammation / etiology
  • Inflammation / immunology
  • Inflammation / metabolism
  • Interferon Regulatory Factors / deficiency
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / metabolism
  • Interleukin-9 / biosynthesis*
  • Interleukin-9 / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Oligonucleotide Array Sequence Analysis
  • T-Lymphocyte Subsets / classification*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Helper-Inducer / classification*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Transcription, Genetic


  • BATF protein, human
  • Basic-Leucine Zipper Transcription Factors
  • Batf protein, mouse
  • IL9 protein, human
  • Interferon Regulatory Factors
  • Interleukin-9
  • interferon regulatory factor-4

Associated data

  • GEO/GSE44937