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Status |
Public on Oct 01, 2021 |
Title |
JunB regulates the common and lineage-specific transcriptional programs of distinct CD4+ effector T cells |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing
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Summary |
IRF4 is critical for differentiation of various CD4+ effector T cells, such as T helper 1 (Th1), Th2, and Th17 subsets, through interaction with BATF-containing AP-1 heterodimers. A major BATF heterodimeric partner, JunB, regulates Th17 differentiation, but the role of JunB in other CD4+ effector T subsets is not fully understood. Here we demonstrate that JunB is essential for accumulation of Th1 and Th2 cells, as well as Th17 cells, both in vitro and in vivo. In mice immunized with lipopolysaccharide (LPS), papain, or complete Freund’s adjuvant (CFA), that induce predominantly Th1, Th2 and Th17 cells, respectively, accumulation of antigen-primed, Junb-deficient CD4+ T cells is significantly impaired. Loss of JunB decreases viability of cells activated under Th1-, Th2-, and Th17-polarizing conditions. RNA-sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) reveal that JunB directly regulates expression of various genes that are commonly induced in priming of naïve CD4+ T cells, including a pro-apoptotic gene Bcl2l11 (encoding Bim), and genes that are specifically induced in Th1, Th2, and Th17 cells. Furthermore, JunB colocalizes with BATF and IRF4 at genomic regions for approximately half of JunB direct target genes. Taken together, JunB, in collaboration with BATF and IRF4, serves a critical function in differentiation of diverse CD4+ T cells by controlling common and lineage-specific gene expression.
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Overall design |
mRNA profiles of naïve CD4+ T cells collected from Junbfl/fl (WT) and Junbfl/flCd4cre mice (JunB KO) and cultured under Th0, th1 and Th17 polarizing conditions for 48h.
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Contributor(s) |
Hsieh T, Sasaki D, Chien H, Ishikawa H |
Citation(s) |
35837408 |
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Submission date |
Apr 21, 2021 |
Last update date |
Jul 20, 2022 |
Contact name |
Hiroki Ishikawa |
E-mail(s) |
oist.ishikawa@gmail.com
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Organization name |
Okinawa Institute of Science and Technology Graduate University
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Street address |
1919-1 Tancha
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City |
Onna son |
State/province |
Okinawa |
ZIP/Postal code |
9040495 |
Country |
Japan |
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Platforms (2) |
GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (28)
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Relations |
BioProject |
PRJNA723553 |
SRA |
SRP315717 |
Supplementary file |
Size |
Download |
File type/resource |
GSE172490_RAW.tar |
17.3 Mb |
(http)(custom) |
TAR (of TXT) |
GSE172490_TPM_Th0_2.csv.gz |
896.7 Kb |
(ftp)(http) |
CSV |
GSE172490_TPM_Th1_2.csv.gz |
885.8 Kb |
(ftp)(http) |
CSV |
GSE172490_TPM_Th2_2.csv.gz |
986.9 Kb |
(ftp)(http) |
CSV |
GSE172490_Th0_2.csv.gz |
1021.6 Kb |
(ftp)(http) |
CSV |
GSE172490_Th1_2.csv.gz |
1020.7 Kb |
(ftp)(http) |
CSV |
GSE172490_Th2_2.csv.gz |
1.0 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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