|
| Status |
Public on Aug 31, 2019 |
| Title |
Lack of NFATc1 SUMOylation protects from inflammatory diseases |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Post-translational modification with SUMO is known to regulate the activity of transcription factors, but how SUMOylation of individual proteins might influence immunity is mostly unexplored. NFATc1 is a transcription factor of the family of ‘Nuclear Factors of Activated T-cells’ which plays an essential role in antigen receptor-mediated gene regulation. It is expressed in multiple isoforms of which the longer isoforms can be modified by SUMOylation. SUMO modification of NFATc1 represses IL-2 in vitro, but its role in T cell-mediated immune responses in vivo is not clear. To this end, we generated a novel Nfatc1 transgenic mouse with lysine to arginine mutations, which abolish the SUMO modification within NFATc1’s C-terminal domain. Inhibition of NFATc1 SUMOylation ameliorated experimental autoimmune encephalomyelitis as well as graft-versus-host disease. This was due to elevated IL-2 production that promoted Treg expansion and suppressed autoreactive or alloreactive T cells. Mechanistically, increased IL-2 secretion counteracted IL-17 and IFN-γ expression through STAT5 and Blimp-1 induction. Blimp-1 also repressed IL-2 itself and the as well induced survival factor Bcl2A1. Still, lack of NFATc1 sumoylation fine-tunes T-cell responses towards lasting tolerance implying a novel approach to treat inflammatory diseases.
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| |
|
| Overall design |
CD4+ CD90.1+ T cells from GvHD-induced mice on d4. CD4+ T cells were either of WT (3 samples) or NFATc1/ΔS (3 samples) genotype
|
| Web link |
https://doi.org/10.1084/jem.20181853
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| |
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| Contributor(s) |
Klein-Hessling S, Klein M, Dietz L, Qureischi M, Friederike B |
| Citation(s) |
32986812 |
| |
| Submission date |
Aug 31, 2018 |
| Last update date |
Apr 14, 2021 |
| Contact name |
Stefan Klein-Hessling |
| E-mail(s) |
stefan.klein-hessling@mail.uni-wuerzburg.de
|
| Phone |
+49 931 3181179
|
| Organization name |
University of Würzburg
|
| Department |
Institute of Pathology
|
| Lab |
Molecular Pathology
|
| Street address |
Josef-Schneider-Str. 2
|
| City |
Würzburg |
| ZIP/Postal code |
97072 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (6)
|
| GSM3369721 |
1.WT CD4+ CD90.1+ T cells (replicate 1) |
| GSM3369722 |
2.WT CD4+ CD90.1+ T cells (replicate 2) |
| GSM3369723 |
3.WT CD4+ CD90.1+ T cells (replicate 3) |
| GSM3369724 |
4.NFATc1/ΔS CD4+ CD90.1+ T cells (replicate 1) |
| GSM3369725 |
5.NFATc1/ΔS CD4+ CD90.1+ T cells (replicate 2) |
| GSM3369726 |
6.NFATc1/ΔS CD4+ CD90.1+ T cells (replicate 3) |
|
| Relations |
| BioProject |
PRJNA488727 |
| SRA |
SRP159242 |
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