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| Status |
Public on Jun 09, 2023 |
| Title |
Mapping Ahr in in vitro differentiated resident memory CD8+ T cells |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The networks of transcription factors (TFs) that control multipotency versus effector programs in intestinal resident memory T (TRM) cells are poorly understood. Mice with post-activation, conditional deletion of the TF Bcl11b in CD8+ T cells, infected with a food-born pathogen, had increased numbers of intestinal TRM cells, and their precursors and decreased splenic effector cells and circulating memory cells and precursors. Loss of circulating memory cells was in part due to increased intestinal homing of Bcl11b-/- circulating precursors with no major alterations in their programs. Bcl11b-/- memory CD8+ T cells had an impaired recall response despite their accumulation in the gut. Intestinal Bcl11b-/- TRM cells and their precursors manifested major alterations in the residency program, with diminished expression of multipotency program genes and upregulation of the effector program genes. Integration of transcriptomics with chromatin accessibility, activating histone marks and Bcl11b genome binding showed a link between the reduction in the multipotent program genes with regions of decreased chromatin accessibility and activating histone marks in Bcl11b-/- cells. In contrast, the effector program genes displayed increased activating epigenetic status. We propose that Bcl11b regulates tissue resident TRM program genes and is positioned upstream of Tcf1 and Blimp1 in regulation of multipotency versus effector TRM program, respectively. Rescuing experiments normalized the increased numbers of intestinal Bcl11b-/- TRM cells. Thus, Bcl11b is a frontrunner in the memory tissue residency program and acts early in lineage decision, promoting TRM cell multipotency and restricting effector function.
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| Overall design |
Examination of Ahr binding in wild type and Bcl11b-deficient CD8+ Trm-like cells
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| Contributor(s) |
Zelenka T, Cismasiu VB, Shaw TI, Avram D |
| Citation(s) |
37115913 |
| |
| Submission date |
Jan 14, 2023 |
| Last update date |
Sep 08, 2023 |
| Contact name |
Dorina Avram |
| E-mail(s) |
dorina.avram@moffitt.org
|
| Organization name |
Moffitt Cancer Center
|
| Department |
Department of Immunology
|
| Lab |
Avram lab
|
| Street address |
12902 Magnolia Drive, MRC4
|
| City |
Tampa |
| State/province |
Fl |
| ZIP/Postal code |
33612 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE186907 |
Regulation of CD8+ T cell differentiation by the transcription factor Bcl11b |
|
| Relations |
| BioProject |
PRJNA923822 |
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