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| Status |
Public on Oct 06, 2023 |
| Title |
The gene expression profile of CD4 T-cells with STAT3 gain-of-function and loss-of-function mutations |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Purpose: Recently discovered activating Interleukin-6 receptor subunit beta (IL6ST, encoding glycoprotein 130 (gp130)) mutations, as well as germline Signal transducer and activator of transcription 3 (STAT3) gain-of-function mutations are associated with multi-organ autoimmunity, severe morbidity, and adverse prognosis, resulting in an unmet medical need.
Methods: To decipher the crucial cellular subsets and disease biology associated with STAT3 gain-of-function mutations, we examined the gene expression profile of STAT3 gain-of-function and loss-of-function mutations in unstimulated, IL10- or IL21-stimulated CD4 T cells and compared them to healthy donor cells.
Results: Activating gp130 signaling in vivo resulted in fatal early-onset multi-organ autoimmunity, resembling numerous clinical features of human STAT3 gain-of-function disease. We observed strong T-cell activation and effector differentiation, accompanied by TH17 expansion and interferon-gamma production. Transcriptome profiling of murine CD4+ and CD8+ T-cells revealed commonly dysregulated genes and a STAT3 gain-of-function signature that was used to discriminate between STAT3 gain-of-function and healthy control patients.
Conclusions: Hyperactive gp130/STAT3 signaling leads to strong TH17-mediated autoimmunity phenotypically resembling human STAT3 gain-of-function disease and identify TH17-cells as a key cellular subset for initiation and maintenance of autoimmunity
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| Overall design |
gene expression profile of STAT3 gain-of-function and loss-of-function mutations in unstimulated, IL10- or IL21-stimulated CD4 T cells and compared them to healthy donor cells.
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| Contributor(s) |
Faletti L, Baumgartner F, Bamopoulos SA, Ramamoorthy S, Ehl S |
| Citation missing |
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| |
| Submission date |
Mar 18, 2022 |
| Last update date |
Oct 07, 2023 |
| Contact name |
Senthilkumar Ramamoorthy |
| E-mail(s) |
senthilkumar.ramamoorthy@uniklinik-freiburg.de
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| Phone |
+49 761 270-46 670
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| Organization name |
UNIVERSITAETSKLINIKUM FREIBURG
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| Street address |
Mathildenstraße 1
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| City |
Freiburg |
| ZIP/Postal code |
79106 |
| Country |
Germany |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (29)
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| Relations |
| BioProject |
PRJNA817580 |
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