ArticleJCI insight2022
A human STAT3 gain-of-function variant confers T cell dysregulation without predominant Treg dysfunction in mice.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Advancements in Diagnosis and Care for Immune Dysregulation and Inborn Errors of Immunity in Pediatric Rheumatology: Our 50-Year Journey.Arthritis care & research · 2026Review
- Impaired regulation by purinergic signaling axis contributes to CD8+ T cell dysregulation in STAT3 gain of function.JCI insight · 2026Article
- Targeted deep sequencing identifies mosaicism in patients with immune dysregulation.The Journal of allergy and clinical immunology · 2026Article
- A case report of ADMIO type 1 caused by aFrontiers in immunology · 2026Article
- STAT3 SH2 Domain Aspartic Acid 661 Mutations Activate Immune Gene Programs.Journal of cellular and molecular medicine · 2026Article
- Inborn errors of regulatory T-cell differentiation and function.The Journal of allergy and clinical immunology · 2025Review
- Y665F variant of mouse Stat5b protects against acute kidney injury through transcriptomic shifts in renal gene expression.Scientific reports · 2025Article
- Mouse Model of STAT3 Mutation Resulting in Job's Syndrome Diverges from Human Pathology.International journal of molecular sciences · 2025Article
- Functional validation of a novel STAT3 'variant of unknown significance' identifies a new case of STAT3 GOF syndrome and reveals broad immune cell defects.Clinical and experimental immunology · 2025Article
- A human STAT3 gain-of-function variant drives local Th17 dysregulation and skin inflammation in mice.The Journal of experimental medicine · 2024Article
- STAT5B SH2 variants disrupt mammary enhancers and the stability of genetic programs during pregnancy.bioRxiv : the preprint server for biology · 2024Article
- JAK inhibitors to treat STAT3 gain-of-function: a single-center report and literature review.Frontiers in immunology · 2024Review
- Differential Diagnosis: Hepatic Complications in Inborn Errors of Immunity.Journal of clinical medicine · 2023Review
- JAKs and STATs from a Clinical Perspective: Loss-of-Function Mutations, Gain-of-Function Mutations, and Their Multidimensional Consequences.Journal of clinical immunology · 2023Review
- Deficiencies and Dysregulation of STAT Pathways That Drive Inborn Errors of Immunity: Lessons from Patients and Mouse Models of Disease.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- The ups and downs of STAT3 function: too much, too little and human immune dysregulation.Clinical and experimental immunology · 2023Review
- STAT3 gain-of-function syndrome.Frontiers in pediatrics · 2022Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
Primary immune regulatory disorders (PIRD) represent a group of disorders characterized by immune dysregulation, presenting with a wide range of clinical disease, including autoimmunity, autoinflammation, or lymphoproliferation. Autosomal dominant germline gain-of-function (GOF) variants in STAT3 result in a PIRD with a broad clinical spectrum. Studies in patients have documented a decreased frequency of FOXP3+ Tregs and an increased frequency of Th17 cells in some patients with active disease. However, the mechanisms of disease pathogenesis in STAT3 GOF syndrome remain largely unknown, and treatment is challenging. We developed a knock-in mouse model harboring a de novo pathogenic human STAT3 variant (p.G421R) and found these mice developed T cell dysregulation, lymphoproliferation, and CD4+ Th1 cell skewing. Surprisingly, Treg numbers, phenotype, and function remained largely intact; however, mice had a selective deficiency in the generation of iTregs. In parallel, we performed single-cell RNA-Seq on T cells from STAT3 GOF patients. We demonstrate only minor changes in the Treg transcriptional signature and an expanded, effector CD8+ T cell population. Together, these findings suggest that Tregs are not the primary driver of disease and highlight the importance of preclinical models in the study of disease mechanisms in rare PIRD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.