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.
View: Text | PDF
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

×

Figure 6

BATF in T cells is required for the development of allergic inflammation.

Options: View larger image (or click on image) Download as PowerPoint
BATF in T cells is required for the development of allergic inflammation...
(A–C) CD4+ T cells from wild-type or BATF-deficient mice were transferred into RAG-deficient recipients. Recipients were challenged i.n. with OVA and TSLP as described in Methods before analysis of pulmonary inflammation. (A) Cell numbers from the BAL (average ± SEM of 7 to 9 mice). (B) Airway histology from mice. Top panels are stained with H&E. Bottom panels are stained for mucus production with PAS. Original magnification, ×40. (C) ELISA analysis of cytokine concentration in the BAL (top) or in supernatants from OVA-stimulated mediastinal lymph node cells (bottom). (D–G) Wild-type and BATF-deficient OTII cells were polarized in vitro under Th9 conditions and transferred into wild-type recipients before daily i.n. challenges with OVA and TSLP for 5 days and subsequent analysis of pulmonary inflammation. (D) Cell numbers from the BAL (average ± SEM of 7 to 8 mice). (E) Airway histology from mice treated as indicated. Top panels show cells stained with H&E. Bottom panels show cells stained for mucus production with PAS. Original magnification, ×40. (F) ELISA analysis of cytokine concentration in the BAL (top) or in supernatants from OVA-stimulated mediastinal lymph node cells (bottom). (G) Quantification of OTII cells from mediastinal lymph node before (D0) and after (D3) OVA stimulation by flow cytometry (contour plots; graph indicates the average ± SEM of all samples). Eos, eosinophils; Neuts, neutrophils; Mϕ, macrophages; Lym, lymphocytes. *P < 0.05; **P < 0.01; ***P < 0.0001.