ArticleArthritis & rheumatology (Hoboken, N.J.)2016
Regulation of Effector Treg Cells in Murine Lupus.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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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.
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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
13 citing papers in PubMed, 20 citations in OpenAlex.
- ROCK1 promotes B cell differentiation and proteostasis under stress through the heme-regulated proteins, BACH2 and HRI.JCI insight · 2025Article
- Interferon Regulatory Factor 4 dose-dependently controls peripheral Treg cell differentiation and homeostasis by modulating chromatin accessibility in mice.Frontiers in immunology · 2025Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- Article
- Role of Dynamic Actin Cytoskeleton Remodeling in Foxp3Frontiers in immunology · 2022Article
- Altered function and differentiation of age-associated B cells contribute to the female bias in lupus mice.Nature communications · 2021Article
- Genome-wide association study in a Korean population identifies six novel susceptibility loci for rheumatoid arthritis.Annals of the rheumatic diseases · 2020Article
- T-Cell Compartmentalization and Functional Adaptation in Autoimmune Inflammation: Lessons From Pediatric Rheumatic Diseases.Frontiers in immunology · 2019Review
- Tregs in SLE: an Update.Current rheumatology reports · 2018Review
- Lymphocyte Autophagy in Homeostasis, Activation, and Inflammatory Diseases.Frontiers in immunology · 2018Review
- Regulation of systemic autoimmunity and CD11cCellular immunology · 2017Review
- Regulatory T Cell and Forkhead Box Protein 3 as Modulators of Immune Homeostasis.Frontiers in immunology · 2017Review
- Regulatory T Cells in SLE: Biology and Use in Treatment.Current rheumatology reports · 2016Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveTreg cells need to acquire an effector phenotype to function in settings of inflammation. Whether effector Treg cells can limit disease severity in lupus is unknown. Interferon regulatory factor 4 (IRF-4) is an essential controller of effector Treg cells and regulates their ability to express interleukin-10 (IL-10). In non-Treg cells, IRF-4 activity is modulated by interactions with DEF-6 and its homolog switch-associated protein 70 (SWAP-70). Although mice lacking both DEF-6 and SWAP-70 (double-knockout [DKO] mice) develop lupus, they display normal survival, suggesting that in DKO mice, Treg cells can moderate disease development. The purpose of this study was to investigate whether Treg cells from DKO mice have an increased capacity to become effector Treg cells due to the ability of DEF-6 and SWAP-70 to restrain IRF-4 activity.
methodsTreg cells were evaluated by fluorescence-activated cell sorting. The B lymphocyte-induced maturation protein 1 (BLIMP-1)/IL-10 axis was assessed by crossing DKO mice with BLIMP-1-YFP-10BiT dual-reporter mice. Deletion of IRF-4 in Treg cells from DKO mice was achieved by generating FoxP3(Cre) IRF-4(fl/fl) DKO mice.
resultsThe concomitant absence of DEF-6 and SWAP-70 led to increased numbers of Treg cells, which acquired an effector phenotype in a cell-intrinsic manner. In addition, Treg cells from DKO mice exhibited enhanced expression of the BLIMP-1/IL-10 axis. Notably, DKO effector Treg cells survived and expanded as disease progressed. The accumulation of Treg cells from DKO mice was associated with the up-regulation of genes controlling autophagy. IRF-4 was required for the expansion and function of effector Treg cells from DKO mice.
conclusionThis study revealed the existence of mechanisms that, by acting on IRF-4, can fine-tune the function and survival of effector Treg cells in lupus. These findings suggest that the existence of a powerful effector Treg cell compartment that successfully survives in an unfavorable inflammatory environment could limit disease development.
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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.