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 5

BATF is required for Th9 differentiation in human T cells.

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BATF is required for Th9 differentiation in human T cells. (A) Naive hum...
(A) Naive human CD4+ T cells isolated by nonatopic or atopic infants were differentiated under Th9 polarizing conditions. After 5 days of culture, RNA was isolated and BATF mRNA was determined using qRT-PCR (n = 5–8). (B) Naive human T cells were differentiated under conditions for each of the indicated subsets. After 2 weeks of differentiation, RNA was isolated to assess the expression of the indicated genes by qRT-PCR. (C–G) Naive human CD4+ T cells were differentiated under Th9 (C and D), Th1 (E), Th2 (F), or Th17 (G) conditions and transfected with control or BATF-specific siRNA. After 5 to 6 days of differentiation, cells were stimulated with anti-CD3, and RNA was isolated for the assessment of gene expression by qRT-PCR (C and E–G), or supernatants were assessed for IL-9 production by ELISA (D). Results represent the average of values from four donors. *P < 0.05; **P < 0.01; ***P < 0.0001.