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Status |
Public on Jul 28, 2015 |
Title |
Transcription factor Bcl11b controls identity and function of mature innate lymphoid cells type II |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Type-2 innate lymphoid cells (ILC2s) promote anti-helminth responses and contribute to allergies. Though Bcl11b has been previously considered a T-lineage identity transcription factor (TF) that restrains the innate-cell genetic programs, we report here that Bcl11b is highly expressed in mature ILC2s and acts upstream of the key ILC2 TFs Gfi1, Gata-3, and of IL-33 receptor IL1rl1 (T1ST2). Additionally, Bcl11b-/- ILC2s de-repressed Rorγt, Ahr and IL-23 receptor, normally expressed in type-3 ILCs (ILC3s). Consequently, Bcl11b-/- ILC2s lost ILC2 functions and gained ILC3 functions, expanding in response to the protease allergen papain, however producing IL-17 and IL-22, and not IL-5 and IL-13, causing lung neutrophilia rather than eosinophilia, and diminished mucus production. Our results broaden Bcl11b's role from a T-cell only TF, and establishes that Bcl11b sustains mature ILC2 genetic and functional programs and lineage fidelity through positive regulation of essential ILC2 TFs and negative regulation of pivotal ILC3 TFs.
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Overall design |
RNA-seq analysis on sorted ILC2s from the mLNs of Bcl11bF/F Cre-ERT2 and wildtype mice at steady state following tamoxifen mediated deletion of Bcl11b
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Contributor(s) |
Califano D, Avram D |
Citation(s) |
26231117 |
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Submission date |
Mar 30, 2015 |
Last update date |
Jul 29, 2019 |
Contact name |
dorina avram |
E-mail(s) |
avramd@mail.amc.edu
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Phone |
518-262-6731
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Organization name |
albany medical college
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Department |
center for immunology and microbial disease
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Street address |
47 new scotland ave
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City |
albany |
ZIP/Postal code |
12208 |
Country |
USA |
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Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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Samples (2) |
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Relations |
BioProject |
PRJNA279899 |
SRA |
SRP056712 |
Supplementary file |
Size |
Download |
File type/resource |
GSE67437_KO-ILC2-mLN_021815_vs_WT-ILC2-mLN_021815.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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