Affinage

FOXP3

Forkhead box protein P3 · UniProt Q9BZS1

Length
431 aa
Mass
47.2 kDa
Annotated
2026-06-09
100 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FOXP3 is a forkhead-domain transcription factor that serves as the central determinant of regulatory T (Treg) cell suppressive identity, and whose loss-of-function mutations cause fatal X-linked multi-organ autoimmunity (XLAAD/IPEX) (PMID:11120765, PMID:32499641). Through its forkhead domain it localizes to the nucleus, binds DNA, and represses transcription from forkhead-motif reporters (PMID:11483607), and it achieves much of its in vivo specificity by assembling higher-order multimers on TnG-repeat microsatellites: cryo-EM reveals a ladder-like architecture in which paired FOXP3 subunits bridge two DNA duplexes, an arrangement disrupted by intra-rung interface mutations that impair DNA bridging and cellular function without affecting canonical motif binding (PMID:38030726). FOXP3 acts as both repressor and context-dependent activator by recruiting chromatin-modifying partners and signal-responsive co-factors; suppressive function specifically requires physical interaction with the acetyltransferase TIP60/KAT5, and the recurrent IPEX mutation p.A384T selectively abolishes TIP60 binding while sparing cytokine repression (PMID:28783662), whereas in activated and tumor-infiltrating Tregs enhanced FOXP3-chromatin binding depends on NFAT and the AP-1 factor Batf (PMID:38935023). Beyond gene regulation, FOXP3 is both necessary and sufficient to program elevated oxidative phosphorylation and fatty acid oxidation, reprogramming Treg metabolism and protecting cells from lipid-induced death (PMID:28194435). FOXP3 expression and protein stability are controlled by multiple layers: TET2/TET3-mediated demethylation of the CNS1/CNS2 elements stabilizes expression (PMID:26903244), Smad3/NFAT and Runx/CBFβ drive its induction and maintenance (PMID:18157133, PMID:19841090), and a reciprocal USP22/RNF20 ubiquitin switch sets FOXP3 protein levels, with USP22 loss causing destabilization and autoimmunity rescuable by RNF20 ablation (PMID:32499641). Lineage-tracing demonstrates that FOXP3 is necessary for suppression of Th17 programs and colitis but is not solely sufficient for all peripheral Treg suppressive features (PMID:35700740).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2000 High

    Establishing that FOXP3 mutations cause heritable autoimmunity defined the gene as a non-redundant guardian of immune tolerance and motivated all subsequent mechanistic work.

    Evidence Positional-candidate cloning and mutation identification in XLAAD kindreds, including a forkhead-truncating splice mutation and a leucine-zipper-disrupting deletion

    PMID:11120765

    Open questions at the time
    • Did not define FOXP3's molecular activity or cellular mechanism of suppression
    • Causal cell type (Tregs) not yet established
  2. 2001 High

    First biochemical characterization showed FOXP3 is a forkhead-domain transcriptional repressor that dampens T cell activation, framing it as a negative regulator of effector responses.

    Evidence Reporter assays with domain mutagenesis in heterologous cells plus overexpression in primary CD4+ T cells with cytokine/proliferation readouts

    PMID:11483607

    Open questions at the time
    • Endogenous target genes not identified
    • Did not address activator functions or cofactor requirements
    • Mechanism of repression unresolved
  3. 2007 High

    Identifying Smad3 and NFAT as enhancer-dependent inducers explained how TGF-β signaling installs FOXP3 expression during Treg differentiation.

    Evidence Enhancer reporter assays and ChIP for histone acetylation in TGF-β-stimulated primary T cells

    PMID:18157133

    Open questions at the time
    • Did not address maintenance of expression after induction
    • Direct FOXP3 protein function not examined
  4. 2009 High

    Runx/CBFβ was shown to both initiate and maintain Foxp3 and to partner with FOXP3 protein, revealing a feed-forward loop linking induction to downstream gene control.

    Evidence ChIP of Runx/CBFβ at the Foxp3 locus plus dominant-negative Runt domain in inducible Treg differentiation

    PMID:19841090

    Open questions at the time
    • Specific shared target genes of the Runx-FOXP3 complex not enumerated
    • Structural basis of cooperation unknown
  5. 2009 Medium

    Acetylation of FOXP3 protein itself was implicated in suppressive function, linking HDAC activity to FOXP3 promoter binding at IL-2.

    Evidence HDAC inhibitor (TSA) treatment of Tregs with FOXP3 acetylation and IL-2 promoter ChIP readouts

    PMID:19172156

    Open questions at the time
    • Mechanism inferred from inhibitor studies rather than direct deacetylase identification
    • Specific acetylated residues not mapped
  6. 2011 Medium

    Cancer-cell studies extended FOXP3's role to tumor suppression via a miRNA feed-forward loop targeting SATB1.

    Evidence 3'-UTR luciferase reporters and miRNA expression analysis with FOXP3 perturbation in breast cancer cells

    PMID:21743493

    Open questions at the time
    • Single cell type, single lab
    • Relevance to Treg biology unclear
  7. 2012 Medium

    FOXP3 was shown to directly regulate proliferation genes (p21, c-MYC) in glioblastoma stem-like cells, supporting a context-dependent tumor-suppressive transcriptional program.

    Evidence ChIP at p21 and c-MYC loci with knockdown/overexpression and xenograft readouts

    PMID:23888189

    Open questions at the time
    • Single cell type
    • Direct vs indirect regulation incompletely resolved
  8. 2015 Medium

    Hormonal and additional tumor-context studies (AR binding at Foxp3; CD44 repression) broadened the regulatory inputs and direct targets of FOXP3.

    Evidence ChIP for AR at the Foxp3 locus with histone H4 acetylation readout; luciferase/ChIP/EMSA for FOXP3 at CD44 with in vivo metastasis assay

    PMID:25683728 PMID:26063731

    Open questions at the time
    • AR-FOXP3 axis limited to single lab
    • Physiological context of cancer-cell FOXP3 expression debated
  9. 2016 High

    TET2/TET3-mediated demethylation of CNS1/CNS2 was established as the epigenetic basis for stable FOXP3 expression, explaining heritable Treg lineage commitment.

    Evidence Tet2/Tet3 double-knockout mice with bisulfite sequencing of Foxp3 CNS regions and vitamin C pharmacological potentiation

    PMID:26903244

    Open questions at the time
    • How demethylation is targeted to specific CNS elements not fully defined
    • Connection to upstream signaling incomplete
  10. 2016 Medium

    FOXP3 in pancreatic cancer cells was shown to trans-activate CCL5, illustrating an activator function that shapes the tumor immune microenvironment.

    Evidence ChIP/luciferase for FOXP3 at the CCL5 promoter plus migration and syngeneic tumor models with CCL5 neutralization

    PMID:27991933

    Open questions at the time
    • Single lab
    • Cofactors enabling activation not defined
  11. 2017 High

    FOXP3 was shown to directly program Treg metabolism, reframing it as a driver of cellular energetics, not only transcription.

    Evidence Seahorse metabolic analysis and proteomics with FOXP3 gain- and loss-of-function in T cells

    PMID:28194435

    Open questions at the time
    • Direct metabolic target genes not enumerated
    • Link between metabolic state and suppression mechanistically incomplete
  12. 2017 High

    Identifying the FOXP3-TIP60 interaction as essential for suppression separated FOXP3's suppressive function from its cytokine-repressive function and explained a recurrent IPEX mutation.

    Evidence Patient-derived Tregs carrying p.A384T, Co-IP of FOXP3-TIP60, suppression assays, and allosteric modifier rescue

    PMID:28783662

    Open questions at the time
    • Genome-wide consequences of TIP60 recruitment not mapped
    • Structural detail of interface limited
  13. 2018 Medium

    Direct FOXP3 repression of VEGF connected its tumor-suppressive activity to angiogenesis control.

    Evidence ChIP/luciferase for FOXP3 at the VEGF promoter with HUVEC tube formation assay in breast cancer cells

    PMID:29970908

    Open questions at the time
    • Single lab, single cancer type
  14. 2020 High

    A reciprocal USP22/RNF20 ubiquitin switch was defined as the post-translational rheostat setting FOXP3 protein abundance and Treg suppressive integrity.

    Evidence CRISPR pooled screen in primary Tregs, Treg-specific Usp22 knockout, and Rnf20/Usp22 double-knockout epistasis rescue with in vivo autoimmunity readouts

    PMID:32499641

    Open questions at the time
    • Direct ubiquitination sites on FOXP3 not mapped here
    • How signaling tunes the switch unknown
  15. 2020 Medium

    HDAC10 was identified as a negative regulator of Treg suppressive function, extending acetylation-based control to in vivo tolerance.

    Evidence HDAC10 knockout mice in adoptive colitis and cardiac allograft tolerance models with in vitro suppression assays

    PMID:31949209

    Open questions at the time
    • Direct FOXP3 acetylation substrate relationship not demonstrated
    • Single lab
  16. 2021 Medium

    lncRNA MALAT1 was shown to shield FOXP3 from STUB1-mediated degradation by competitive domain masking, adding an RNA-based layer of protein stabilization.

    Evidence Co-IP and domain mapping of MALAT1-FOXP3, STUB1 ubiquitination assay, and FOXP3 ChIP at GINS1

    PMID:33972684

    Open questions at the time
    • lncRNA-protein interaction methods have inherent limitations
    • Single lab; physiological relevance in Tregs untested
  17. 2022 High

    Lineage tracing dissected FOXP3-dependent from FOXP3-independent peripheral Treg features, showing FOXP3 is necessary but not solely sufficient for all suppressive functions.

    Evidence Genetic lineage tracing and Foxp3-deficient pTreg fate mapping with colitis and mastocytosis readouts

    PMID:35700740

    Open questions at the time
    • Identity of FOXP3-independent suppressive determinants unresolved
    • Molecular basis of FOXP3-independent persistence unknown
  18. 2023 High

    The cryo-EM structure of FOXP3 multimers on TnG repeats revealed a ladder-like DNA-bridging architecture, explaining its broad in vivo specificity and the functional cost of forkhead-interface mutations.

    Evidence Cryo-EM structure determination with intra-rung interface mutagenesis and in vitro/in vivo DNA-binding and cellular functional assays

    PMID:38030726

    Open questions at the time
    • How multimer assembly is regulated in cells not addressed
    • Link between specific multimers and target gene choice unresolved
  19. 2024 High

    FOXP3 chromatin engagement was shown to be dynamically remodeled by activation state and microenvironment through NFAT/Batf, establishing a signal-responsive logic to its genomic occupancy.

    Evidence CUT&RUN/ChIP under multiple activation conditions, proximity proteomics, and genetic/pharmacological perturbation of NFAT and Batf

    PMID:38935023

    Open questions at the time
    • Full proximity interactome not exhaustively defined
    • Causal link between dynamic binding and suppressive output incomplete
  20. 2024 High

    Lag3 was shown to restrain Myc-dependent metabolic reprogramming to preserve FOXP3+ Treg function, integrating co-receptor signaling with the metabolic program FOXP3 establishes.

    Evidence Treg-specific Lag3-mutant mice with RNA-seq, metabolic profiling, and PI3K/Rictor/Ldha pathway inhibition in an autoimmunity model

    PMID:39236718

    Open questions at the time
    • Direct interplay between Lag3 signaling and FOXP3 protein not defined
    • How metabolic state feeds back on FOXP3 activity unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FOXP3 multimer composition, cofactor recruitment (TIP60, NFAT/Batf), post-translational switches, and metabolic programming are integrated into a single coherent gene-regulatory output remains unresolved.
  • No unified model linking structure-defined multimers to specific target gene selection
  • Mechanism coupling metabolic reprogramming to transcriptional output unknown
  • FOXP3-independent suppressive determinants in pTregs unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 1
Pathway
R-HSA-168256 Immune System 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1430728 Metabolism 2
Partners
BATFCBFBMALAT1NFATRUNXSMAD3STUB1TIP60

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 FOXP3 (Scurfin) requires its forkhead domain for nuclear localization and DNA binding. When transiently expressed in heterologous cells, FOXP3 represses transcription from a reporter containing multimeric forkhead binding sites. Overexpression in CD4+ T cells attenuates activation-induced cytokine production and proliferation. FKH binding sequences were identified adjacent to NFAT regulatory sites in promoters of cytokine genes sensitive to FOXP3 abundance. Transient transfection of heterologous cells with reporter assay, domain mutagenesis, overexpression in CD4+ T cells with cytokine/proliferation readouts The Journal of biological chemistry High 11483607
2000 Loss-of-function mutations in FOXP3 (JM2), including a splice junction mutation producing a truncated protein lacking the forkhead domain, and an in-frame 3-bp deletion predicted to impair a leucine zipper dimerization domain, cause X-linked autoimmunity-allergic dysregulation syndrome (XLAAD) with Th2 skewing and multi-system autoimmunity. Positional-candidate gene cloning, mutation identification in two kindreds, analysis of T cell phenotype The Journal of clinical investigation High 11120765
2007 Smad3 and NFAT are required for activity of a FOXP3 enhancer element, and both factors are essential for histone acetylation in the enhancer region and induction of FOXP3 expression. This was established using a model system with primary T cells and biochemical analysis of the enhancer. Enhancer reporter assay, chromatin immunoprecipitation for histone acetylation, primary T cell system with TGF-β stimulation Nature immunology High 18157133
2009 Runx proteins regulate both the initiation and maintenance of Foxp3 gene expression. Runx/core-binding factor beta binds regulatory elements within the Foxp3 locus. Full-length Runx promoted de novo Foxp3 expression during inducible Treg differentiation; a dominant-negative Runt DNA-binding domain antagonized de novo Foxp3 expression. Runx proteins and Foxp3 form a feed-forward loop in which Runx drives Foxp3 expression and then cooperates with Foxp3 protein to regulate downstream target genes. ChIP showing Runx/CBFβ binding at Foxp3 locus, dominant-negative Runt domain functional assay, inducible Treg differentiation assay The Journal of experimental medicine High 19841090
2016 TET2 and TET3 enzymes mediate loss of 5-methylcytosine at Treg-specific hypomethylated regions including CNS1 and CNS2 of the Foxp3 locus during thymic Treg development, stabilizing Foxp3 expression. In Tet2/Tet3 double-deficient mice, stability of Foxp3 expression is markedly compromised, phenocopying CNS2-deficient Treg cells. Vitamin C potentiates TET activity through Tet2/Tet3 to increase Foxp3 stability in TGF-β-induced Tregs. Tet2/Tet3 double-knockout mice, bisulfite sequencing of Foxp3 CNS1/CNS2, vitamin C treatment with Foxp3 stability readout The Journal of experimental medicine High 26903244
2020 A CRISPR-based pooled screen in primary mouse Tregs identified USP22 (a deubiquitination module member of the SAGA complex) as a positive regulator and RNF20 (an E3 ubiquitin ligase) as a negative regulator of Foxp3 expression. Treg-specific ablation of Usp22 reduced Foxp3 protein levels and caused suppressive function defects leading to spontaneous autoimmunity. Foxp3 destabilization in Usp22-deficient Tregs was rescued by ablation of Rnf20, revealing a reciprocal ubiquitin switch. CRISPR pooled screen in primary Tregs, Treg-specific Usp22 knockout mice, Rnf20/Usp22 double knockout rescue, in vivo autoimmunity and tumor growth models Nature High 32499641
2023 FOXP3 uses its forkhead domain to form higher-order multimers upon binding to TnG repeat microsatellites. Cryo-EM structure reveals a ladder-like architecture with two double-stranded DNA molecules as 'side rails' bridged by five pairs of FOXP3 molecules. Each FOXP3 subunit binds TGTTTGT within the repeats identically to binding the forkhead consensus motif (TGTTTAC). Mutations in the intra-rung interface impair TnG repeat recognition, DNA bridging, and cellular functions without affecting binding to the canonical forkhead motif. FOXP3 tolerates variable inter-rung spacings explaining broad in vivo specificity for TnG-repeat-like sequences. Cryo-EM structure determination, intra-rung interface mutagenesis, DNA binding assays in vitro and in vivo, cellular functional assays Nature High 38030726
2017 FOXP3 is both necessary and sufficient to program increased oxidative phosphorylation (OXPHOS) capacity and fatty acid oxidation in Tregs. Using metabolic analysis and proteomics, Foxp3 drives upregulation of components of all electron transport chain complexes, increasing their activity and ATP generation. This results in selective protection of Foxp3+ cells from fatty acid-induced cell death. Metabolic analysis (Seahorse), mass spectrometry-based proteomics, Foxp3 gain- and loss-of-function in T cells JCI insight High 28194435
2017 FOXP3-mediated suppression in human Tregs requires physical interaction between FOXP3 and the histone acetyltransferase TIP60 (KAT5). The common IPEX mutation p.A384T abrogates the suppressive capacity of Tregs while preserving FOXP3's ability to repress inflammatory cytokine production. This selective functional impairment is due to specific disruption of FOXP3-A384T binding to TIP60. The defect can be corrected using allosteric modifiers that enhance FOXP3–TIP60 interaction. Patient-derived Treg cells with IPEX mutation characterization, co-immunoprecipitation of FOXP3–TIP60 interaction, suppression assays, allosteric modifier rescue Science immunology High 28783662
2009 HDAC inhibitor trichostatin A increases Foxp3+ Treg suppressive function at least in part by promoting acetylation of Foxp3 protein itself. Acetylation of Foxp3 is required for effective binding of Foxp3 to the IL-2 gene promoter and suppression of IL-2 expression. Class II HDAC activity (but not class I alone) is critical for this regulation. HDAC inhibitor treatment of Tregs, protein acetylation analysis, ChIP/promoter binding assay for IL-2 promoter, in vitro and in vivo suppression assays Immunology and cell biology Medium 19172156
2020 Deletion of HDAC10 in Tregs increases their suppressive function in vitro and in vivo. HDAC10-deficient Tregs protected Rag1-/- mice from colitis and conferred long-term allograft tolerance in fully MHC-mismatched cardiac transplants, whereas wild-type Tregs did not. This implicates HDAC10-mediated deacetylation as a negative regulator of Foxp3+ Treg suppressive function. HDAC10 knockout mice, adoptive transfer colitis model, cardiac allograft transplant model, in vitro suppression assay Scientific reports Medium 31949209
2015 Androgen receptor binds a functional androgen response element within the Foxp3 locus and modulates Foxp3 expression. AR binding leads to changes in acetylation status of histone H4 at the Foxp3 locus, while methylation of defined CpG regions in the Foxp3 gene is unaffected. ChIP for AR binding at Foxp3 locus, histone H4 acetylation analysis, CpG methylation analysis, functional androgen response element identification Molecular biology of the cell Medium 26063731
2011 FOXP3 directly suppresses SATB1 expression and induces miR-7 and miR-155, which target the 3'-UTR of SATB1, forming a feed-forward regulatory loop. This mechanism operates in breast cancer cells where FOXP3 acts as a tumor suppressor. Luciferase 3'-UTR reporter assay, miRNA expression analysis, FOXP3 overexpression/knockdown in breast cancer cells Oncogene Medium 21743493
2016 FOXP3 expressed in pancreatic ductal adenocarcinoma cancer cells directly trans-activates CCL5 transcription, promoting recruitment of FOXP3+ Treg cells to tumors. This recruitment was impaired by CCL5 neutralization and inhibited tumor growth. ChIP and luciferase reporter assay demonstrating direct FOXP3 binding to CCL5 promoter, in vitro migration assay, syngeneic mouse tumor models with CCL5 neutralization Oncogene Medium 27991933
2018 FOXP3 directly binds the VEGF promoter via forkhead-binding motifs and suppresses VEGF transcription in breast cancer cells, thereby inhibiting angiogenesis. Luciferase reporter assay, ChIP demonstrating FOXP3 binding to VEGF promoter, FOXP3 overexpression in breast cancer cell lines, HUVEC tube formation assay Cell death & disease Medium 29970908
2015 FOXP3 directly binds the CD44 promoter and represses its transcription in breast cancer cells, thereby suppressing adhesion, invasion, and metastasis. This was confirmed by luciferase reporter assay, ChIP, and electrophoretic mobility shift assay. Luciferase reporter assay, ChIP, EMSA, FOXP3 siRNA knockdown and overexpression in breast cancer cells, in vivo metastasis assay International journal of cancer Medium 25683728
2012 FOXP3 acts as a transcriptional regulator of p21 and c-MYC in glioblastoma stem-like cells. ChIP demonstrated direct FOXP3 binding at p21 and c-MYC loci, supporting a mechanism by which FOXP3 loss de-represses these targets to promote tumorigenesis. ChIP for FOXP3 at p21 and c-MYC loci, FOXP3 knockdown and overexpression in glioblastoma neurosphere cells, proliferation and migration assays, xenograft model Oncotarget Medium 23888189
2021 MALAT1 (lncRNA) stabilizes FOXP3 protein by binding to the zinc finger (ZF) and leucine zipper (LZ) domains of FOXP3, masking the same domains used by E3 ligase STUB1 to interact with FOXP3. This prevents STUB1-mediated ubiquitination and degradation of FOXP3. FOXP3 in turn serves as a transcriptional activator of GINS1, defining a MALAT1-FOXP3-GINS1 regulatory axis. Co-immunoprecipitation of MALAT1 with FOXP3, domain mapping of FOXP3 interaction sites, STUB1-FOXP3 ubiquitination assay, FOXP3 ChIP at GINS1 promoter Oncogene Medium 33972684
2024 Foxp3-chromatin binding is dynamically regulated by Treg activation states, tumor microenvironment, and antigen/cytokine stimulations. NFAT and AP-1 transcription factor Batf are required for enhanced Foxp3-chromatin binding in activated Tregs and tumor-infiltrating Tregs. Mutations at the Foxp3 DNA-binding domain destabilize Foxp3-chromatin association. Proteomics revealed dynamic protein interactions within Foxp3 proximity upon TCR or IL-2 receptor signaling, reflecting interactions among Foxp3, signal transducers, and chromatin. CUT&RUN/ChIP for Foxp3-chromatin binding under multiple activation conditions, proximity proteomics, pharmacological inhibition and genetic knockdown of NFAT and Batf, Foxp3 DNA-binding domain mutations The Journal of experimental medicine High 38935023
2024 Lag3, an inhibitory co-receptor expressed on Tregs, supports Foxp3+ Treg suppressive function by restraining Myc-dependent metabolic programming. Treg-specific Lag3 mutation activated the PI3K-Akt-Rictor pathway, elevating Myc expression to levels seen in Th1 effector cells. Inhibition of PI3K, Rictor, or Ldha (a key Myc target) restored normal metabolism and suppressive function in Lag3-mutant Tregs. Treg cell-specific Lag3-mutant mouse models, RNA sequencing, metabolic profiling, pharmacological inhibition of PI3K/Rictor/Ldha, in vivo autoimmunity model Immunity High 39236718
2022 Genetic tracing of peripherally induced Treg cells showed that many distinguishing features of microbiota-induced pTreg cells are Foxp3-independent. Lineage-committed pTreg-like cells persisted in the colon without Foxp3. Foxp3 was critical for suppression of a Th17 cell program, colitis, and mastocytosis, but pTreg cells suppressed colonic effector T cell expansion in a Foxp3-independent manner. Genetic lineage tracing of microbiota-induced pTreg cells, Foxp3-deficient pTreg cell fate mapping, colitis and mastocytosis phenotypic readouts Immunity High 35700740

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 FOXP3: of mice and men. Annual review of immunology 766 16551248
2000 JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. The Journal of clinical investigation 684 11120765
2011 Regulatory T cells and Foxp3. Immunological reviews 661 21488902
2007 Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer. Nature immunology 639 18157133
2019 Human FOXP3+ Regulatory T Cell Heterogeneity and Function in Autoimmunity and Cancer. Immunity 586 30784578
2017 The regulation of immune tolerance by FOXP3. Nature reviews. Immunology 451 28757603
2001 Scurfin (FOXP3) acts as a repressor of transcription and regulates T cell activation. The Journal of biological chemistry 420 11483607
2007 OX40 costimulation turns off Foxp3+ Tregs. Blood 331 17575071
2009 Epigenetic mechanisms of regulation of Foxp3 expression. Blood 300 19641188
2016 Control of Foxp3 stability through modulation of TET activity. The Journal of experimental medicine 286 26903244
2009 Plasticity of CD4(+) FoxP3(+) T cells. Current opinion in immunology 263 19500966
2016 From IPEX syndrome to FOXP3 mutation: a lesson on immune dysregulation. Annals of the New York Academy of Sciences 248 26918796
2012 Differentiation and function of Foxp3(+) effector regulatory T cells. Trends in immunology 217 23219401
2020 CRISPR screen in regulatory T cells reveals modulators of Foxp3. Nature 201 32499641
2019 Regulatory T Cells: the Many Faces of Foxp3. Journal of clinical immunology 190 31478130
2016 Cancer-FOXP3 directly activated CCL5 to recruit FOXP3+Treg cells in pancreatic ductal adenocarcinoma. Oncogene 187 27991933
2014 FOXP3 and scurfy: how it all began. Nature reviews. Immunology 180 24722479
2017 Foxp3 drives oxidative phosphorylation and protection from lipotoxicity. JCI insight 175 28194435
2008 Foxp3 expression in human cancer cells. Journal of translational medicine 172 18430198
2015 Androgen receptor modulates Foxp3 expression in CD4+CD25+Foxp3+ regulatory T-cells. Molecular biology of the cell 156 26063731
2017 Suppressive IL-17A+Foxp3+ and ex-Th17 IL-17AnegFoxp3+ Treg cells are a source of tumour-associated Treg cells. Nature communications 154 28290453
2005 FOXP3 acts as a rheostat of the immune response. Immunological reviews 153 15661028
2009 FOXP3 and the regulation of Treg/Th17 differentiation. Microbes and infection 146 19371792
2017 Flicr, a long noncoding RNA, modulates Foxp3 expression and autoimmunity. Proceedings of the National Academy of Sciences of the United States of America 140 28396406
2011 CD4(+)Foxp3(+) regulatory T cell therapy in transplantation. Journal of molecular cell biology 138 22170955
2010 FOXP3 and RORγt: transcriptional regulation of Treg and Th17. International immunopharmacology 128 21081189
2007 IPEX as a result of mutations in FOXP3. Clinical & developmental immunology 127 18317533
2013 Advances in distinguishing natural from induced Foxp3(+) regulatory T cells. International journal of clinical and experimental pathology 126 23329997
2010 PI3 kinase signalling blocks Foxp3 expression by sequestering Foxo factors. The Journal of experimental medicine 124 20603315
2015 FOXP3(+) Treg Cells and Gender Bias in Autoimmune Diseases. Frontiers in immunology 122 26441996
2010 Human FOXP3 and cancer. Oncogene 114 20498631
2005 IPEX and FOXP3: clinical and research perspectives. Journal of autoimmunity 113 16243487
2006 Cell-surface IL-7 receptor expression facilitates the purification of FOXP3(+) regulatory T cells. Trends in immunology 103 17045841
2017 Foxp3+ Regulatory T Cell Expression of Keratinocyte Growth Factor Enhances Lung Epithelial Proliferation. American journal of respiratory cell and molecular biology 101 28296468
2022 Human FOXP3 and tumour microenvironment. Immunology 99 35689826
2013 ICOS controls Foxp3(+) regulatory T-cell expansion, maintenance and IL-10 production during helminth infection. European journal of immunology 96 23319295
2015 Development of thymic Foxp3(+) regulatory T cells: TGF-β matters. European journal of immunology 95 25684698
2017 IL-17A-Producing Foxp3+ Regulatory T Cells and Human Diseases. Immune network 88 29093649
2011 FOXP3 and FOXP3-regulated microRNAs suppress SATB1 in breast cancer cells. Oncogene 84 21743493
2009 Runx proteins regulate Foxp3 expression. The Journal of experimental medicine 84 19841090
2009 FOXP3 and its role in the immune system. Advances in experimental medicine and biology 82 20429413
2006 FOXP3 and NFAT: partners in tolerance. Cell 81 16873058
2020 The Many Functions of Foxp3+ Regulatory T Cells in the Intestine. Frontiers in immunology 80 33193456
2019 Mechanisms of human FoxP3+ Treg cell development and function in health and disease. Clinical and experimental immunology 79 30864147
2018 Human FOXP3+ T regulatory cell heterogeneity. Clinical & translational immunology 77 29484183
2010 Foxp3(+) cell infiltration and granzyme B(+)/Foxp3(+) cell ratio are associated with outcome in neoadjuvant chemotherapy-treated ovarian carcinoma. Cancer immunology, immunotherapy : CII 77 20087581
2012 Neuropeptides and neuropeptide receptors: drug targets, and peptide and non-peptide ligands: a tribute to Prof. Dieter Seebach. Chemistry & biodiversity 76 23161624
2022 Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Treg cells. Immunity 75 35700740
2009 Using histone deacetylase inhibitors to enhance Foxp3(+) regulatory T-cell function and induce allograft tolerance. Immunology and cell biology 71 19172156
2019 The role of FOXP3+ regulatory T cells in human autoimmune and inflammatory diseases. Clinical and experimental immunology 68 30830965
2012 Foxp3(+) regulatory T cells, immune stimulation and host defence against infection. Immunology 65 22211994
2016 Characterization of Th17 and FoxP3(+) Treg Cells in Paediatric Psoriasis Patients. Scandinavian journal of immunology 64 26679087
2006 FOXP3 ensembles in T-cell regulation. Immunological reviews 63 16903909
2013 FOXP3: genetic and epigenetic implications for autoimmunity. Journal of autoimmunity 62 23313429
2019 The expression of FOXP3 and its role in human cancers. Biochimica et biophysica acta. Reviews on cancer 60 30630091
2009 Identification and characterization of Foxp3(+) gammadelta T cells in mouse and human. Immunology letters 60 19539651
2020 HDAC10 deletion promotes Foxp3+ T-regulatory cell function. Scientific reports 57 31949209
2011 The molecular mechanisms of Foxp3 gene regulation. Seminars in immunology 56 21752667
2018 FOXP3 inhibits angiogenesis by downregulating VEGF in breast cancer. Cell death & disease 55 29970908
2011 Nature and nurture in Foxp3(+) regulatory T cell development, stability, and function. Human immunology 55 22240298
2015 The immunosuppressive enzyme IL4I1 promotes FoxP3(+) regulatory T lymphocyte differentiation. European journal of immunology 52 25778793
2011 FOXP3+ regulatory T cells: control of FOXP3 expression by pharmacological agents. Trends in pharmacological sciences 51 21237521
2017 Zebrafish FOXP3 is required for the maintenance of immune tolerance. Developmental and comparative immunology 50 28365195
2022 CD4+FoxP3+CD73+ regulatory T cell promotes cardiac healing post-myocardial infarction. Theranostics 49 35401839
2017 Suppression by human FOXP3+ regulatory T cells requires FOXP3-TIP60 interactions. Science immunology 49 28783662
2015 RORγt(+)Foxp3(+) Cells are an Independent Bifunctional Regulatory T Cell Lineage and Mediate Crescentic GN. Journal of the American Society of Nephrology : JASN 49 26054541
2013 Foxp3(+) regulatory T cells in tuberculosis. Advances in experimental medicine and biology 48 23468109
2015 FOXP3 suppresses breast cancer metastasis through downregulation of CD44. International journal of cancer 47 25683728
2015 Clinical Outlook for Type-1 and FOXP3(+) T Regulatory Cell-Based Therapy. Frontiers in immunology 47 26635807
2019 Menopause and FOXP3+ Treg cell depletion eliminate female protection against T cell-mediated angiotensin II hypertension. American journal of physiology. Heart and circulatory physiology 46 31099612
2016 The Role of FOXP3 in Human Cancers. Anticancer research 46 27466478
2015 Ubiquitin-dependent regulation of Foxp3 and Treg function. Immunological reviews 45 26085205
2008 FOXP3 and its partners: structural and biochemical insights into the regulation of FOXP3 activity. Immunologic research 44 18626575
2019 Foxp3+ Regulatory T Cells in Bone and Hematopoietic Homeostasis. Frontiers in endocrinology 43 31551927
2021 MALAT1 modulated FOXP3 ubiquitination then affected GINS1 transcription and drived NSCLC proliferation. Oncogene 42 33972684
2010 Dexamethasone upregulates FOXP3 expression without increasing regulatory activity. Immunobiology 41 20667622
2008 Functional analysis of FOXP3. Annals of the New York Academy of Sciences 39 19076349
2019 Stability and Maintenance of Foxp3+ Treg Cells in Non-lymphoid Microenvironments. Frontiers in immunology 36 31798580
2012 Degradation of polycyclic aromatic hydrocarbons by Pseudomonas sp. JM2 isolated from active sewage sludge of chemical plant. Journal of environmental sciences (China) 36 23534211
2013 The role of FOXP3 in regulating immune responses. International reviews of immunology 35 23947341
2019 Glucocorticoid Receptor-Deficient Foxp3+ Regulatory T Cells Fail to Control Experimental Inflammatory Bowel Disease. Frontiers in immunology 32 30936873
2018 Chitotriosidase inhibits allergic asthmatic airways via regulation of TGF-β expression and Foxp3+ Treg cells. Allergy 32 29420850
2010 Transcriptional regulation of Foxp3 in regulatory T cells. Immunobiology 32 21122941
2005 FoxP3: a genetic link between immunodeficiency and autoimmune diseases. Autoimmunity reviews 32 16890893
2020 FoxP3, CTLA-4, and IDO in Canine Melanocytic Tumors. Veterinary pathology 31 33021155
2023 Acidity-mediated induction of FoxP3+ regulatory T cells. European journal of immunology 30 36788428
2023 FOXP3 recognizes microsatellites and bridges DNA through multimerization. Nature 30 38030726
2010 CD4 (+)CD25 (+)Foxp3 (+) regulatory T cells and hematologic malignancies. Frontiers in bioscience (Scholar edition) 30 20515837
2024 Inhibitory co-receptor Lag3 supports Foxp3+ regulatory T cell function by restraining Myc-dependent metabolic programming. Immunity 29 39236718
2021 Induction of stable human FOXP3+ Tregs by a parasite-derived TGF-β mimic. Immunology and cell biology 29 33929751
2012 Helios expression in FoxP3(+) T regulatory cells. Expert opinion on biological therapy 29 22827571
2024 The FOXP3+ Pro-Inflammatory T Cell: A Potential Therapeutic Target in Crohn's Disease. Gastroenterology 28 38211712
2015 Downregulation of FOXP3 inhibits invasion and immune escape in cholangiocarcinoma. Biochemical and biophysical research communications 28 25623530
2021 Coexpression of Helios in Foxp3+ Regulatory T Cells and Its Role in Human Disease. Disease markers 27 34257746
2016 The role of FOXP3 in autoimmunity. Current opinion in immunology 27 27544816
2020 IL-34 Actions on FOXP3+ Tregs and CD14+ Monocytes Control Human Graft Rejection. Frontiers in immunology 26 32849510
2012 FOXP3, a novel glioblastoma oncosuppressor, affects proliferation and migration. Oncotarget 25 23888189
2018 FoxP3 and IDO in Canine Melanocytic Tumors. Veterinary pathology 24 30381008
2024 Dynamic Foxp3-chromatin interaction controls tunable Treg cell function. The Journal of experimental medicine 23 38935023
2022 Tissue Resident Foxp3+ Regulatory T Cells: Sentinels and Saboteurs in Health and Disease. Frontiers in immunology 23 35359918

Missed literature

Know a paper Affinage missed for FOXP3? Flag it for the maintainers and the community.

No submissions yet.