Th9 cell development requires a BATF-regulated transcriptional network
Rukhsana Jabeen, … , Baohua Zhou, Mark H. Kaplan
Rukhsana Jabeen, … , Baohua Zhou, Mark H. Kaplan
Published October 8, 2013
Citation Information: J Clin Invest. 2013;123(11):4641-4653. https://doi.org/10.1172/JCI69489.
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Th9 cell development requires a BATF-regulated transcriptional network

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.

Authors

Rukhsana Jabeen, Ritobrata Goswami, Olufolakemi Awe, Aishwarya Kulkarni, Evelyn T. Nguyen, Andrea Attenasio, Daniel Walsh, Matthew R. Olson, Myung H. Kim, Robert S. Tepper, Jie Sun, Chang H. Kim, Elizabeth J. Taparowsky, Baohua Zhou, Mark H. Kaplan

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Figure 1

Microarray analysis of the Th9 transcriptional signature.

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Microarray analysis of the Th9 transcriptional signature. Naive CD4+ T c...
Naive CD4+ T cells were differentiated under Th2, Th9, or iTreg polarizing conditions for 5 days before RNA was isolated for microarray analysis. (A) Heatmap comparison of transcript levels in Th2, Th9, and iTreg cells. Hierarchical clustering was performed using a Pearson’s correlation with MeV software. (B) Graphical representation of 629 genes that were enriched in Th9 cells at least 2-fold compared with Th2 or iTreg cells. Genes were subdivided as enriched in Th9 cells by 5-fold (indicated by “>>”) or enriched by 2- to 5-fold (indicated by “>”) compared with the other Th subsets. (C) Heatmap of selected genes in Th9, Th2, and iTreg cells. Genes were selected based on functions that include transcription factors, cytokines, and surface receptors. Clustering was performed using Manhattan distance analysis.