Abstract
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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Basic-Leucine Zipper Transcription Factors / deficiency
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Basic-Leucine Zipper Transcription Factors / genetics
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Basic-Leucine Zipper Transcription Factors / metabolism*
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Cell Lineage / genetics
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Cell Lineage / immunology
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Humans
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Hypersensitivity / etiology
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Hypersensitivity / immunology
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Hypersensitivity / metabolism
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Hypersensitivity, Immediate / genetics
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Hypersensitivity, Immediate / immunology
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Hypersensitivity, Immediate / metabolism
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Infant
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Inflammation / etiology
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Inflammation / immunology
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Inflammation / metabolism
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Interferon Regulatory Factors / deficiency
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Interferon Regulatory Factors / genetics
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Interferon Regulatory Factors / metabolism
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Interleukin-9 / biosynthesis*
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Interleukin-9 / genetics
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Oligonucleotide Array Sequence Analysis
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T-Lymphocyte Subsets / classification*
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocytes, Helper-Inducer / classification*
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
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Transcription, Genetic
Substances
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BATF protein, human
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Basic-Leucine Zipper Transcription Factors
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Batf protein, mouse
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IL9 protein, human
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Interferon Regulatory Factors
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Interleukin-9
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interferon regulatory factor-4