|
| Status |
Public on Sep 13, 2013 |
| Title |
Specification of innate type-2 lymphocytes by the transcriptional determinant Gfi1 |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Innate type-2 lymphoid cells (ILC2s) function in immune responses against helminth parasites and are implicated in allergic inflammation and asthma. ILC2s are activated by the epithelial-derived cytokines IL-33 and IL-25 and are major sources of the type-2 cytokines IL-5 and IL-13. We show that the transcription factor Gfi1 promotes the generation of ILC2s and controls their responsiveness during Nippostrongylus brasiliensis infection as well as IL-33- or IL-25-instigated inflammation. Gfi1 directly activates Il1rl1, which encodes the IL-33 receptor. IL- 33 signaling upregulates Gfi1, thereby constituting a positive feedback loop that enables rapid and robust expansion of ILC2s in response to IL-33 signaling. Loss of Gfi1 in activated ILC2s results in an unusual effector state involving derepression of the IL-17 inflammatory program and co-expression of IL-13 with IL-17. ChIPseq reveals key Gfi1 targeted genes that are activated or repressed to maintain ILC2 identity. We propose that Gfi1 functions as a shared determinant within innate and adaptive immune cells to specify type-2 responses, while actively repressing the IL-17 effector state.
|
| |
|
| Overall design |
ILC2s (~3 x 10^7 cells) were sorted from the MLN of IL-25-treated mice. Chromatin fragments bound by Gfi1 were subject to ChIP using Gfi1 antibodies and followed by high-throughput sequencing.
|
| |
|
| Contributor(s) |
Spooner CJ, Khan AA, Singh H |
| Citation(s) |
24141388 |
| Submission date |
Sep 12, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Aly Azeem Khan |
| Organization name |
University of Chicago
|
| Street address |
6045 S. Kenwood Ave.
|
| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60637 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
|
| Samples (2) |
|
| Relations |
| BioProject |
PRJNA219059 |
| SRA |
SRP029908 |
