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| Status |
Public on Jan 05, 2012 |
| Title |
Functional and epigenetic studies reveal multistep differentiation and plasticity of in vitro and in vivo follicular T helper cells |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Follicular T helper cells (Tfh) provide critical help to B cells for germinal center (GC) formation. Mutations affecting SLAM-associated Protein (SAP) prevent GC formation due to defective T-B cell interactions, yet effects on Tfh cell differentiation remain unclear. We describe the in vitro differentiation of functionally-competent “Tfh-like” cells that expressed Interleukin-21, Tfh markers, and Bcl6, and rescued GC formation in SAP-deficient hosts better than other T helper (Th) cells. SAP-deficient Tfh-like cells appeared virtually indistinguishable from wildtype, yet failed to support GCs in vivo. Interestingly, both Tfh-like and in vivo-derived Tfh cells could produce effector cytokines in response to polarizing conditions. Moreover, Th1, Th2 and Th17 cells could be reprogrammed to obtain Tfh characteristics. ChIP-Seq analyses revealed positive epigenetic markings on Tbx21, Gata3 and Rorc in Tfh-like and ex vivo Tfh cells, and Bcl6 in other Th cell populations, supporting the concept of plasticity between Tfh and other Th cells.
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| Overall design |
Epigenetic modifications were evaluated in ChIP-Seq studies by profiling histone H3K4 and H3K27 trimethylation marks between Th1, Th2, Th17, Tfh-like, and CXCR5+PD-1+ sorted Tfh-like in vitro generated T helper cell populations and ex vivo derived Tfh cells.
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| Contributor(s) |
Lu KT, Kanno Y, Sun H, O'Shea JJ, Schwartzberg PL |
| Citation(s) |
22018472 |
| Submission date |
Oct 11, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Yuka Kanno |
| E-mail(s) |
kannoy@mail.nih.gov
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| Phone |
301-402-3008
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| Organization name |
NIH
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| Department |
NIAMS
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| Lab |
LCBS-MIIB
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| Street address |
10 Center Drive, Rm13C120
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892-1930 |
| Country |
USA |
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| Platforms (1) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
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| Samples (12)
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| Relations |
| SRA |
SRP008800 |
| BioProject |
PRJNA146549 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE32864_RAW.tar |
38.5 Mb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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