 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jan 11, 2021 |
| Title |
The TGF-β superfamily cytokine Activin-A is induced during autoimmune neuroinflammation and drives pathogenic Th17 cell differentiation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Th17 cells are known to exert pathogenic and non-pathogenic functions. Although the cytokine transforming growth factor β1 (TGF-β1) is instrumental for Th17 cell differentiation, it is dispensable for generation of pathogenic Th17 cells. Here, we examined the T cell-intrinsic role of Activin-A, a TGF-β superfamily member closely related to TGF-β1, in pathogenic Th17 cell differentiation. Activin-A expression was increased in individuals with relapsing-remitting multiple sclerosis and in mice with experimental autoimmune encephalomyelitis. Stimulation with interleukin-6 and Activin-A induced a molecular program that mirrored that of pathogenic Th17 cells and was inhibited by blocking Activin-A signaling. Genetic disruption of Activin-A and its receptor ALK4 in T cells impaired pathogenic Th17 cell differentiation in vitro and in vivo. Mechanistically, extracellular-signal-regulated kinase (ERK) phosphorylation, which was essential for pathogenic Th17 cell differentiation, was suppressed by TGF-β1-ALK5 but not Activin-A-ALK4 signaling. Thus, Activin-A drives pathogenic Th17 cell differentiation, implicating the Activin-A-ALK4-ERK axis as a therapeutic target for Th17 cell-related diseases.
|
| |
|
| Overall design |
A: mRNA profiles of CA-ALK4 and CA-ALK5 transduced Th17 cells in the presence of IL-6 were generated by deep sequencing, in triplicate, using BGI’s unique DNBseq™.
B: mRNA profiles of Th17 cells differentiated by IL-1b+IL-6+IL-23, TGFb1+IL-6 and Activin A+IL-6 were generated by deep sequencing, in triplicate, using BGI’s unique DNBseq™.
C: mRNA profiles of Th17 cells differentiated by IL-1b+IL-6+IL-23, IL-1b+IL-6+IL-23+anti-Activin-A were generated by deep sequencing, in triplicate, using BGI?s unique DNBseq.
D: mRNA profiles of T cells differentiated by IL-6, IL-6+ Activin-A were generated by deep sequencing, in triplicate, using BGI?s unique DNBseq.
|
| |
|
| Contributor(s) |
Wu B, Li P, Xu X, Li JL, Wan Y |
| Citation(s) |
33421362 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AI123193 |
Functional protein networks underlying T cell growth, proliferation and differentiation |
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL |
Yisong Wan |
| R01 AI160774 |
TGF-b superfamily signaling in controlling Th17 cell function in autoimmune neuroinflammation |
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL |
Yisong Wan |
|
| Submission date |
Jun 01, 2020 |
| Last update date |
Jan 13, 2021 |
| Contact name |
Yisong Wan |
| Organization name |
University of North Carolina-Chapel Hill
|
| Department |
Lineberger Comprehensive Cancer Center
|
| Lab |
Marsico Hall Rm 5229J
|
| Street address |
125 Mason Farm Road
|
| City |
Chapel Hill |
| State/province |
NC |
| ZIP/Postal code |
27599 |
| Country |
USA |
| |
|
| Platforms (1) |
|
| Samples (48)
|
|
| Relations |
| BioProject |
PRJNA636293 |
| SRA |
SRP265456 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE151533_Th17_CA_ALK_DESeq2_normalizedCounts.txt.gz |
980.7 Kb |
(ftp)(http) |
TXT |
| GSE151533_Th17_CA_ALK_featureCounts.txt.gz |
510.6 Kb |
(ftp)(http) |
TXT |
| GSE151533_Th17_Day1_DESeq2_normalizedCounts.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
| GSE151533_Th17_Day1_featureCounts.txt.gz |
617.2 Kb |
(ftp)(http) |
TXT |
| GSE151533_Th17_Day1b_DESeq2_normalizedCounts.txt.gz |
1.6 Mb |
(ftp)(http) |
TXT |
| GSE151533_Th17_Day1b_featureCounts.txt.gz |
751.3 Kb |
(ftp)(http) |
TXT |
| GSE151533_Th17_Day2_DESeq2_normalizedCounts.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
| GSE151533_Th17_Day2_featureCounts.txt.gz |
621.9 Kb |
(ftp)(http) |
TXT |
| GSE151533_Th17_Day2b_DESeq2_normalizedCounts.txt.gz |
1.6 Mb |
(ftp)(http) |
TXT |
| GSE151533_Th17_Day2b_featureCounts.txt.gz |
754.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...