Th9 cell development requires  a BATF-regulated transcriptional network.
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.
Rukhsana
R
Jabeen
Ritobrata
R
Goswami
Olufolakemi
O
Awe
Aishwarya
A
Kulkarni
Evelyn T
ET
Nguyen
Andrea
A
Attenasio
Daniel
D
Walsh
Matthew R
MR
Olson
Myung H
MH
Kim
Robert S
RS
Tepper
Jie
J
Sun
Chang H
CH
Kim
Elizabeth J
EJ
Taparowsky
Baohua
B
Zhou
Mark H
MH
Kaplan
D019264:Adoptive Transfer; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D006969:Hypersensitivity, Immediate / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007223:Infant; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D016906:Interleukin-9 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D016176:T-Lymphocyte Subsets / Q000145:classification* / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification* / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic; D000099218:Interferon Regulatory Factor-4
D050976:Basic-Leucine Zipper Transcription Factors; D050835:Interferon Regulatory Factors; D016906:Interleukin-9; D000099218:Interferon Regulatory Factor-4; C099359:BATF protein, human; C431772:Batf protein, mouse; C508607:IL9 protein, human