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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Research Article Immunology

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 2

Expression and function of the Th9 gene signature.

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Expression and function of the Th9 gene signature. Naive CD4 T cells wer...
Naive CD4 T cells were differentiated under polarizing conditions to generate the indicated Th subsets. (A) RNA was isolated from Th subsets for expression analysis of the indicated genes using qRT-PCR. Expression is relative to naive CD4+ T cells and normalized to β-2 microglobulin expression. (B) Flow cytometric analysis of CD103 expression on the surface of Th subsets. Numbers indicate the average percentage ± SD of positive cells from at least three experiments. (C) Flow cytometric analysis of CCR4 expression on the surface of Th subsets. Numbers indicate the average percentage ± SD of positive cells from at least three experiments. (D) Chemotaxis assay of Th2 and Th9 cell response to increasing concentrations of CCL22. Migrated cells after 4 hours of incubation were counted in a hemacytometer. Results indicate the average ± SD of triplicate determinations and are representative of three experiments. (E) The concentration of IL-1RA was determined in the supernatant 24 hours following anti-CD3 stimulation of the indicated Th subsets. Results are the average ± SD of three experiments. (F) Naive CD4+ T cells were cultured under Th9 polarizing conditions in the absence (DMSO, vehicle) or presence of FICZ at the indicated concentration. IL-9 concentration was determined 24 hours after anti-CD3 stimulation. *P < 0.05.