Affinage

IL21R

Interleukin-21 receptor · UniProt Q9HBE5

Length
538 aa
Mass
59.1 kDa
Annotated
2026-06-10
42 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL-21R is a class I cytokine receptor that couples IL-21 binding to JAK/STAT signaling to control B-cell and T-cell fate decisions across humoral immunity, anti-viral responses, and autoimmunity (PMID:16391014, PMID:19478140, PMID:36800413). Its extracellular domain carries a C-mannose modification at the first tryptophan of the WSXWS motif, where a sugar chain bridges the two fibronectin type III domains to convert the receptor from a V-shaped to an A-frame architecture; this bridge forms independently of ligand and is required for export of IL-21R and the common γ-chain to the plasma membrane, explaining why WSXWS mutations cause primary immunodeficiency (PMID:22235133, PMID:26043171). Ligand engagement triggers JAK1/JAK3 autophosphorylation and tyrosine phosphorylation of STAT1, STAT3, and STAT5, and intact downstream JAK/STAT signaling—not mere surface expression—is required for IL-21 responses, as JAK3-deficient cells remain refractory despite abundant receptor (PMID:16391014, PMID:20193734, PMID:39884449). The cellular outcome of signaling is strictly context-dependent: in naïve B cells and CLL/follicular lymphoma cells IL-21R drives caspase-dependent, Bim-mediated apoptosis, whereas in pre-activated, class-switched, and germinal-center B cells it promotes proliferation, isotype switching, and antibody-secreting-cell formation, with signal amplitude tuned by PTEN [PMID:16391014, PMID:20193734, PMID:40795247, PMID:bio_10.1101_2024.07.13.600808]. In germinal centers, combined IL-21R and CD40 signaling synergistically induces c-MYC and phospho-S6 to drive plasma-cell and memory-precursor differentiation as a distinct positive-selection pathway (PMID:36800413). In T cells, cell-autonomous IL-21R signaling sustains CD8+ T-cell proliferation and IFN-γ production during chronic infection and tissue inflammation, supports pathogenic Th17 generation by maintaining IL-23R, drives effector CD4+ differentiation in GVHD, and intrinsically restrains IL-17-producing γδ T cells (PMID:19478140, PMID:26413871, PMID:22465422, PMID:20574002, PMID:25849970). IL-21R abundance is set transcriptionally by SP1 binding to its promoter, post-transcriptionally by miR-30a targeting its 3'UTR, and at the mRNA level by IFN-α/β-mediated down-regulation (PMID:30233580, PMID:27006279, PMID:15178704).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2004 Medium

    Established that IL-21R responsiveness is dynamically controlled by type I interferon, linking innate cytokine context to the strength of IL-21/STAT3 signaling in NK and T cells.

    Evidence RT-PCR, Western blot, and EMSA of STAT phosphorylation and DNA binding after IFN-α/β treatment

    PMID:15178704

    Open questions at the time
    • Mechanism of IFN-α/β-driven IL-21R mRNA down-regulation not defined
    • No in vivo confirmation of the regulatory axis
  2. 2006 High

    Showed that IL-21R engages canonical JAK1/JAK3-STAT1/3/5 signaling yet drives apoptosis rather than proliferation in malignant B cells, revealing the context-dependence of receptor output.

    Evidence Phosphorylation and caspase-cleavage Western blots and flow cytometry in CD40-stimulated primary CLL B cells

    PMID:16391014

    Open questions at the time
    • Does not explain what cellular context switches output from apoptosis to proliferation
    • Pro-apoptotic vs pro-survival determinants downstream of STATs unresolved
  3. 2006 Medium

    Identified an IL-21R polymorphism (T-83C) altering IL-21-induced IFN-γ output and IgE suppression, providing the first genotype-function link for receptor variation.

    Evidence Ex vivo cytokine assays, Cε promoter reporter, germline mRNA measurement, and genotype correlation

    PMID:17015683

    Open questions at the time
    • Molecular mechanism by which the polymorphism alters signaling unknown
    • Single-cohort genotype correlation
  4. 2007 Medium

    Demonstrated in vivo that IL-21R is required for IL-21-dependent isotype switching and antibody-secreting-cell differentiation, and that its blockade dampens autoantibody-driven disease.

    Evidence IL-21R.Fc fusion blockade in lupus-prone MRL-Fas(lpr) mice with autoantibody and B-cell function readouts

    PMID:17339481

    Open questions at the time
    • Pharmacological blockade does not isolate B-cell-intrinsic from extrinsic effects
    • Downstream transcriptional program not defined
  5. 2008 High

    Extended IL-21R function beyond lymphocytes by showing it controls dendritic-cell CCR7 upregulation and MMP2-dependent migration to lymph nodes during skin inflammation.

    Evidence Il21r-/- mice, bone-marrow reconstitution, adoptive transfer, CCR7 flow cytometry, and MMP2 activation assay

    PMID:19075398

    Open questions at the time
    • Direct signaling link between IL-21R and CCR7/MMP2 induction not mapped
    • Whether DC effect is fully cell-intrinsic not resolved
  6. 2009 High

    Defined a cell-autonomous, context-restricted T-cell role: IL-21R sustains CD8+ T-cell proliferation and cytokine production specifically during chronic, but not acute, viral infection.

    Evidence Il21r-/- mice and adoptive transfer during LCMV infection with T-cell phenotype/function readouts

    PMID:19478140

    Open questions at the time
    • Molecular basis for chronic-specific dependence unknown
    • Transcriptional targets sustaining CD8+ persistence not identified
  7. 2010 Medium

    Established that functional JAK/STAT signaling downstream of IL-21R, not surface expression, determines responsiveness, by showing JAK3-deficient lymphoma cells resist IL-21 apoptosis.

    Evidence JAK/STAT and SOCS3 analysis and apoptosis assays in JAK3-defective vs responsive lymphoma lines

    PMID:20193734

    Open questions at the time
    • Single cell-line comparison
    • SOCS3 role in setting response threshold not functionally tested
  8. 2010 Medium

    Showed donor T-cell-intrinsic IL-21R signaling drives effector CD4+ differentiation and GVHD pathology independently of regulatory T cells.

    Evidence Allogeneic BMT with Il21r-/- splenocytes, CD25-depletion controls, MLR, cytokine and histopathology readouts

    PMID:20574002

    Open questions at the time
    • Transcriptional effector program downstream of IL-21R not defined
    • Single-model GVHD setting
  9. 2012 High

    Solved the IL-21:IL-21R structure, revealing C-mannosylation at the WSXWS motif and a sugar bridge that converts the receptor into an A-frame architecture.

    Evidence X-ray crystallography of the IL-21:IL-21R complex with structural validation

    PMID:22235133

    Open questions at the time
    • Did not test functional requirement of the sugar bridge
    • Glycosylation enzymology in cells not addressed
  10. 2012 Medium

    Confirmed cell-autonomous IL-21R signaling in CD8+ T cells drives IFN-γ production required for CVB3 myocarditis, generalizing the chronic-inflammation CD8+ dependence.

    Evidence Adoptive transfer of IL-21RKO vs WT CD8+ T cells into CD8KO recipients with disease scoring

    PMID:22465422

    Open questions at the time
    • Single disease model
    • Signaling intermediates linking IL-21R to IFN-γ not mapped
  11. 2015 High

    Connected the structural sugar bridge to function and disease by showing it forms ligand-independently and that WSXWS mutations block IL-21R/γc plasma-membrane export, explaining immunodeficiency.

    Evidence Crystal structure of unbound IL-21R plus mutagenesis and cell-surface trafficking assays

    PMID:26043171

    Open questions at the time
    • Cellular C-mannosyltransferase machinery not identified
    • Quantitative impact on signaling output not measured
  12. 2015 Medium

    Identified IL-21R as a driver of pathogenic Th17 cells by maintaining IL-23R expression, linking it to autoimmune neuroinflammation.

    Evidence Il21r deletion in 2D2xTH transgenic EAE mice with Th17 and IL-23R flow cytometry and disease scoring

    PMID:26413871

    Open questions at the time
    • Direct mechanism maintaining IL-23R unknown
    • Single transgenic model
  13. 2015 Medium

    Revealed an opposing T-cell role: intrinsic IL-21R signaling suppresses IL-17-producing γδ T cells in the respiratory tract, highlighting cell-type-specific outcomes.

    Evidence IL-21R KO mice in influenza A infection with γδ/Th17 flow cytometry and BAL cytokines

    PMID:25849970

    Open questions at the time
    • Mechanism of γδ T-cell suppression unknown
    • Whether suppression is direct on γδ cells not fully resolved
  14. 2016 Medium

    Established post-transcriptional control of IL-21R by miR-30a targeting its 3'UTR, with receptor overexpression rescuing Th17 differentiation.

    Evidence Dual luciferase 3'UTR reporter, miR-30a overexpression, IL-21R rescue, and EAE model

    PMID:27006279

    Open questions at the time
    • Physiological signals controlling miR-30a not defined
    • In vivo contribution of this axis to receptor levels not quantified
  15. 2017 Medium

    Extended IL-21R signaling to the myeloid compartment, showing overexpression on myeloma-associated monocytes promotes JAK-dependent osteoclast differentiation.

    Evidence Profiling of sorted BM CD14+ monocytes, ex vivo osteoclastogenesis, and Janex-1 JAK inhibition

    PMID:28057743

    Open questions at the time
    • STAT effectors in osteoclast program not defined
    • Single patient-derived system
  16. 2018 Medium

    Identified SP1 as a direct transcriptional activator of IL21R whose increased promoter binding amplifies pSTAT3 signaling and plasmablast differentiation in rheumatoid arthritis B cells.

    Evidence ChIP-qPCR for SP1 at the IL21R promoter with pSTAT3, plasmablast, and IL-6 readouts

    PMID:30233580

    Open questions at the time
    • Upstream signals driving SP1 recruitment unknown
    • Correlative link between SP1 binding and disease activity
  17. 2021 Medium

    Linked chromatin regulation to IL-21R expression, showing Cbx3/HP1γ loss opens the Il21r locus and that IL-21R is required for enhanced anti-tumor CD8+ T-cell persistence.

    Evidence Cbx3/HP1γ KO CD8+ T cells, chromatin/ChIP-seq, and multiple in vivo tumor models

    PMID:34721405

    Open questions at the time
    • Direct epigenetic mechanism at the locus not fully resolved
    • Relative contribution of IL-21R vs LEF-1 not separated
  18. 2023 High

    Defined IL-21R + CD40 as a distinct germinal-center positive-selection pathway that synergistically induces c-MYC and phospho-S6 to drive plasma-cell and memory-precursor differentiation.

    Evidence Bulk and single-cell RNA-seq with flow cytometry of GC B cells in vitro and in vivo and signal-combination perturbations

    PMID:36800413

    Open questions at the time
    • Molecular integration of IL-21R and CD40 signals not fully mapped
    • How this pathway interfaces with BCR-based selection unresolved
  19. 2023 Low

    Nominated GTF2I as an additional transcriptional regulator of IL21R based on binding at the upstream/5'UTR region in B cells.

    Evidence ChIP-seq in CD19+ B cells with motif analysis and ENCODE comparison

    PMID:37713154

    Open questions at the time
    • Binding identified without functional validation of transcriptional regulation
    • No perturbation of GTF2I to confirm effect on IL-21R levels
    • Single dataset
  20. 2024 Medium

    Dissected the apoptosis-versus-proliferation switch genetically, showing B-cell-intrinsic IL-21R drives Bim-dependent apoptosis in naïve B cells but proliferation in class-switched B cells and is required for the pre-GC-to-GC transition.

    Evidence Conditional Il21r KO mice with ex vivo culture, immunization, and apoptosis assays (preprint)

    PMID:bio_10.1101_2024.07.13.600808

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Molecular determinant gating apoptosis vs proliferation not identified
  21. 2025 Medium

    Established PTEN as a negative regulator of IL-21R signaling amplitude in germinal-center B cells, selectively biasing toward plasma-cell differentiation when relieved.

    Evidence Inducible PTEN deletion in established GC B cells with competitive transfer and flow cytometry

    PMID:40795247

    Open questions at the time
    • Biochemical node where PTEN restrains IL-21R signaling not pinpointed
    • Single-lab GC system
  22. 2025 Medium

    Functionally assigned the intracellular IL-21R domain to STAT3-mediated activation by using a TGF-βRII/IL-21R chimera to convert suppressive signals into NK-cell activation.

    Evidence Domain-swap chimeric receptor with cytotoxicity assays, xenograft models, and JAK-STAT3 readouts

    PMID:39884449

    Open questions at the time
    • Engineered receptor context may not reflect native signaling
    • STAT3-specific vs broader STAT contributions not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single IL-21R/JAK-STAT signal is mechanistically converted into opposing apoptotic versus proliferative outcomes across cell states remains the central unresolved question.
  • No defined molecular switch linking signal amplitude/context to fate decision
  • Differential STAT target gene programs across cell types not catalogued
  • Quantitative role of negative regulators (PTEN, SOCS3, miRNA) in setting thresholds not integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 2
Partners
IL21JAK1JAK3STAT1STAT3STAT5

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 Crystal structure of IL-21 bound to IL-21R revealed that the WSXWS motif of IL-21R is C-mannosylated at the first tryptophan, and a sugar chain bridges the two fibronectin type III domains of IL-21R, anchoring at the WSXWS motif through an extensive hydrogen bonding network including mannosylation, transforming the V-shaped receptor into an A-frame structure. X-ray crystallography of IL-21:IL-21R complex with structural validation The Journal of biological chemistry High 22235133
2015 The sugar bridge connecting the two fibronectin type III domains of IL-21R forms independently of IL-21 binding, and mutations within the WSXWS motif impair export of IL-21R and γc to the plasma membrane, providing a molecular explanation for how WSXWS mutations cause primary immunodeficiency. Crystal structure of unbound IL-21R; mutagenesis and cell-surface expression assays Genes and immunity High 26043171
2006 IL-21R expression on CLL B cells is up-regulated by CD40 triggering; IL-21 signaling through IL-21R induces JAK1, JAK3 autophosphorylation and STAT1, STAT3, STAT5 tyrosine phosphorylation, and promotes apoptosis via caspase-8, caspase-3 activation, Bid cleavage to t-Bid, and PARP and p27Kip-1 cleavage rather than proliferation in CLL B cells. Western blot phosphorylation assays, caspase activity assays, flow cytometry, CD40 stimulation of primary CLL B cells Blood High 16391014
2009 Cell-autonomous IL-21R signaling in CD8+ T cells is required for sustained proliferation and cytokine production during chronic LCMV infection in mice; IL-21R is dispensable for CD8+ T cell expansion, effector function, memory homeostasis, and recall responses during acute/resolved infections. Il21r-/- mouse model, adoptive transfer experiments, flow cytometry for T cell phenotype and function Science (New York, N.Y.) High 19478140
2007 IL-21R-mediated signaling is required for IL-21-dependent isotype switching and differentiation of B cells into antibody-secreting cells; blockade with IL-21R.Fc fusion protein in lupus-prone mice reduced autoantibody production, total IgG, and splenic B lymphocyte function. IL-21R.Fc fusion protein blockade in MRL-Fas(lpr) mice; measurement of autoantibodies, IgG levels, and splenic B cell function ex vivo Journal of immunology (Baltimore, Md. : 1950) Medium 17339481
2008 IL-21R signaling is required for CCR7 upregulation on skin dendritic cells and their migration toward CCR7 ligands; IL-21 treatment of epidermal and dermal cells activates MMP2, which is implicated in skin DC trafficking to draining lymph nodes and subsequent allergic skin inflammation. Il21r-/- mice, Il21r-/- bone marrow reconstitution, adoptive transfer of OVA-specific CD4+ T cells, CCR7 expression by flow cytometry, MMP2 activation assay The Journal of clinical investigation High 19075398
2004 IFN-α/β down-regulates IL-21R mRNA expression in NK and T cells, resulting in reduced STAT3 phosphorylation and DNA binding after IL-21 stimulation; the IL-21 gene promoter contains a putative IFN-gamma activation site (GAS) element that binds STAT1, STAT2, STAT3, and STAT4 in IFN-α/β-stimulated cells. RT-PCR for IL-21R mRNA, Western blot/EMSA for STAT phosphorylation and DNA binding, promoter analysis with gel-shift assays Journal of leukocyte biology Medium 15178704
2006 IL-21 inhibits IL-4-induced IgE production in PBMC/splenocyte cultures through an IFN-γ-dependent mechanism mediated via IL-21R; a polymorphism (T-83C) in the IL-21R gene is associated with lower IL-21-induced IFN-γ production and reduced sensitivity to IL-21-mediated inhibition of IgE. Ex vivo cytokine production assays, gene reporter assay for Cε promoter, germline Cε mRNA measurements, polymorphism genotyping with functional correlation Journal of immunology (Baltimore, Md. : 1950) Medium 17015683
2023 IL-21R plus CD40 signals synergize to induce c-MYC and phospho-S6 in germinal center B cells, engage unique molecular mechanisms distinct from BCR+CD40 signaling, and specifically drive IRF4hi/CD138+ plasma cell differentiation and CCR6+/CD38+ memory B cell precursor formation, revealing a second positive selection pathway in GC B cells. Bulk RNA-seq, single-cell RNA-seq, flow cytometry of GC B cells in vitro and in vivo; signal combination experiments with genetic and pharmacological perturbations Science immunology High 36800413
2015 IL-21R signaling supports generation and stabilization of pathogenic Th17 cells by maintaining IL-23R expression on Th17 cells and expression of key molecules for pathogenic Th17 generation; IL-21R deficiency in 2D2xTH transgenic mice reduced Th17 differentiation and spontaneous EAE incidence and severity. Il21r genetic deletion in 2D2xTH transgenic EAE mice; flow cytometry for Th17 cells and IL-23R expression; disease scoring The Journal of clinical investigation Medium 26413871
2012 IL-21R signaling directly in CD8+ T cells promotes their activation (IFN-γ production) and is required for CVB3-induced myocarditis; this was demonstrated as cell-autonomous by adoptive transfer of IL-21RKO vs. WT CD8+ T cells into CD8KO recipients. IL-21RKO mice, adoptive transfer of purified CD8+ T cells into CD8KO recipients, flow cytometry for CD8+IFN-γ+ cells, myocarditis scoring Experimental and molecular pathology Medium 22465422
2010 IL-21R signaling in donor CD4+ T cells promotes effector T cell differentiation and is required for full GVHD pathology; recipients of IL-21R-deficient CD4+ T cells had reduced inflammatory cell infiltration in liver and intestine, impaired MLR, and reduced cytokine production, with the effect attributable to impaired effector T cell differentiation rather than changes in regulatory T cells. Allogeneic BMT with Il21r-/- splenocytes, CD25 depletion experiments, MLR, cytokine production assays, histopathology Journal of immunology (Baltimore, Md. : 1950) Medium 20574002
2015 IL-21R signaling intrinsically suppresses the accumulation of IL-17-producing γδ T cells in the respiratory tract both at steady state and after influenza A virus infection, without affecting adaptive T cell responses or virus clearance. IL-21R KO mice, influenza A virus infection model, flow cytometry for γδ T cells and Th17 cells, BAL cytokine measurements PloS one Medium 25849970
2010 Defective JAK3 expression in follicular lymphoma cell line DOHH2 results in resistance to IL-21-mediated apoptosis despite high IL-21R surface expression, demonstrating that functional JAK/STAT signaling downstream of IL-21R is required for IL-21-induced apoptosis; IL-21 upregulates SOCS3 in responsive but not refractory cells. Western blot for JAK/STAT phosphorylation, RT-PCR for JAK3 and SOCS3, Annexin-V apoptosis assay, immunofluorescence Experimental hematology Medium 20193734
2017 IL-21R overexpression in CD14+CD16+ bone marrow monocytes from multiple myeloma patients increases osteoclast formation; inhibition of IL-21R signaling with JAK inhibitor Janex-1 suppressed osteoclast differentiation from these monocytes. Flow cytometry and transcriptional profiling of sorted BM CD14+ monocytes; ex vivo osteoclastogenesis cultures; Janex-1 pharmacological inhibition Haematologica Medium 28057743
2018 Increased binding of transcription factor SP1 to the IL21R promoter in RA B cells drives enhanced IL-21R expression, increased pSTAT3 signaling, greater plasmablast differentiation, and elevated IL-6 production in response to IL-21 stimulation. ChIP-qPCR for SP1 binding to IL21R promoter, flow cytometry for IL-21R and pSTAT3, cytokine ELISA, plasmablast differentiation assay Frontiers in immunology Medium 30233580
2021 Targeting Cbx3/HP1γ in CD8+ T cells increases transcriptional activity at the Il21r locus, upregulating IL-21R expression; both LEF-1 and IL-21R are necessary for Cbx3/HP1γ-deficient CD8+ T cells to persist and control tumor growth in vivo. Cbx3/HP1γ KO CD8+ T cells, chromatin remodeling/ChIP-seq analysis, in vivo tumor models (ovarian cancer, melanoma, neuroblastoma), flow cytometry Frontiers in immunology Medium 34721405
2016 miR-30a directly targets the IL-21R 3'UTR (validated by dual luciferase reporter assay), downregulating IL-21R expression to inhibit Th17 differentiation; overexpression of IL-21R reversed the inhibitory effects of miR-30a on Th17 differentiation. Dual luciferase reporter assay, miR-30a overexpression in naïve T cells, IL-21R overexpression rescue experiments, in vivo EAE model Brain, behavior, and immunity Medium 27006279
2025 IL-21R signals through the IL-21R-STAT3/JAK-STAT3 pathway; a chimeric receptor TRII/21R (extracellular TGF-βRII fused to transmembrane and intracellular IL-21R domains) converts TGF-β immunosuppressive signals into NK cell activation signals via the IL-21R-STAT3 pathway, enhancing CAR-NK cell cytotoxicity, proliferation, and survival. Chimeric receptor construct design and expression, in vitro cytotoxicity assays, xenograft mouse tumor models, JAK-STAT3 pathway readouts Pharmacological research Medium 39884449
2025 PTEN negatively regulates IL-21R signaling strength in germinal center B cells; PTEN deletion in established GC B cells results in more sustained IL-21R signaling and enhanced CD40 signaling, selectively promoting plasma cell differentiation without affecting class switching or memory precursor differentiation. Tamoxifen-inducible Cre PTEN deletion in B cells after GC establishment; GC B cell transfer system with WT and PTEN-deficient cells in same recipients; flow cytometry for plasma cell and memory B cell markers Journal of immunology (Baltimore, Md. : 1950) Medium 40795247
2024 B cell-intrinsic IL-21R signaling promotes proliferation of pre-activated/class-switched IgG1+ B cells but induces Bim-dependent apoptosis in naïve B cells; B cell-specific Il21r deletion causes severe defects in IgG1 antibody responses and impairs the transition of B cells from a pre-GC to GC state in vivo. Conditional Il21r KO mouse model, ex vivo B cell culture systems, in vivo immunization, flow cytometry for GC/plasmablast markers, apoptosis assays bioRxivpreprint Medium bio_10.1101_2024.07.13.600808
2023 ChIP-seq analysis identified IL21R as a target gene of GTF2I in CD19+ B cells, with GTF2I binding peaks detected in the upstream region and 5'UTR of the IL21R locus, suggesting GTF2I regulates IL-21R expression at the transcriptional level. ChIP-seq in CD19+ B cells, motif analysis by MEME-ChIP, comparison with ENCODE GTF2I ChIP-seq datasets Hepatology international Low 37713154

Source papers

Stage 0 corpus · 42 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 IL-21R on T cells is critical for sustained functionality and control of chronic viral infection. Science (New York, N.Y.) 374 19478140
2007 IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression. Journal of immunology (Baltimore, Md. : 1950) 248 17339481
2008 IL-21R is essential for epicutaneous sensitization and allergic skin inflammation in humans and mice. The Journal of clinical investigation 96 19075398
2009 A polymorphism within IL21R confers risk for systemic lupus erythematosus. Arthritis and rheumatism 95 19644854
2006 Interleukin-21 receptor (IL-21R) is up-regulated by CD40 triggering and mediates proapoptotic signals in chronic lymphocytic leukemia B cells. Blood 88 16391014
2023 IL-21R signal reprogramming cooperates with CD40 and BCR signals to select and differentiate germinal center B cells. Science immunology 71 36800413
2012 Crystal structure of interleukin-21 receptor (IL-21R) bound to IL-21 reveals that sugar chain interacting with WSXWS motif is integral part of IL-21R. The Journal of biological chemistry 71 22235133
2014 Human IL-21 and IL-21R deficiencies: two novel entities of primary immunodeficiency. Current opinion in pediatrics 60 25321844
2010 RGMA and IL21R show association with experimental inflammation and multiple sclerosis. Genes and immunity 57 20072140
2004 IFN-alpha regulates IL-21 and IL-21R expression in human NK and T cells. Journal of leukocyte biology 54 15178704
2006 IFN-gamma-mediated inhibition of human IgE synthesis by IL-21 is associated with a polymorphism in the IL-21R gene. Journal of immunology (Baltimore, Md. : 1950) 46 17015683
2016 MiR-30a inhibits Th17 differentiation and demyelination of EAE mice by targeting the IL-21R. Brain, behavior, and immunity 36 27006279
2017 IL21R expressing CD14+CD16+ monocytes expand in multiple myeloma patients leading to increased osteoclasts. Haematologica 34 28057743
2018 IL-21R functions as an oncogenic factor and is regulated by the lncRNA MALAT1/miR-125a-3p axis in gastric cancer. International journal of oncology 30 30387833
2015 IL-21R signaling is critical for induction of spontaneous experimental autoimmune encephalomyelitis. The Journal of clinical investigation 30 26413871
2013 IL21 and IL21R polymorphisms and their interactive effects on serum IL-21 and IgE levels in patients with chronic hepatitis B virus infection. Human immunology 26 23354321
2015 A conserved sugar bridge connected to the WSXWS motif has an important role for transport of IL-21R to the plasma membrane. Genes and immunity 23 26043171
2010 IL21R and PTH may underlie variation of femoral neck bone mineral density as revealed by a genome-wide association study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 22 19874204
2012 IL-21R expression on CD8+ T cells promotes CD8+ T cell activation in coxsackievirus B3 induced myocarditis. Experimental and molecular pathology 21 22465422
2010 Heterogeneous expression and function of IL-21R and susceptibility to IL-21-mediated apoptosis in follicular lymphoma cells. Experimental hematology 19 20193734
2014 Elevated frequencies of CD4(+) IL-21(+) T, CD4(+) IL-21R(+) T and IL-21(+) Th17 cells, and increased levels of IL-21 in bleomycin-induced mice may be associated with dermal and pulmonary inflammation and fibrosis. International journal of rheumatic diseases 18 25545680
2025 Chimeric cytokine receptor TGF-β RⅡ/IL-21R improves CAR-NK cell function by reversing the immunosuppressive tumor microenvironment of gastric cancer. Pharmacological research 17 39884449
2015 IL-21R signaling suppresses IL-17+ gamma delta T cell responses and production of IL-17 related cytokines in the lung at steady state and after Influenza A virus infection. PloS one 17 25849970
2022 Altered Circulating Follicular T Helper Cell Subsets and Follicular T Regulatory Cells Are Indicators of a Derailed B Cell Response in Lupus, Which Could Be Modified by Targeting IL-21R. International journal of molecular sciences 16 36293075
2012 Immune activation and increased IL-21R expression are associated with the loss of memory B cells during HIV-1 infection. Journal of internal medicine 14 22530560
2010 Altered effector CD4+ T cell function in IL-21R-/- CD4+ T cell-mediated graft-versus-host disease. Journal of immunology (Baltimore, Md. : 1950) 13 20574002
2021 Targeting Cbx3/HP1γ Induces LEF-1 and IL-21R to Promote Tumor-Infiltrating CD8 T-Cell Persistence. Frontiers in immunology 12 34721405
2016 Impaired coronary microcirculation in type 2 diabetic patients is associated with elevated circulating regulatory T cells and reduced number of IL-21R⁺ T cells. Cardiovascular diabetology 10 27095356
2013 IL-21R gene polymorphisms and serum IL-21 levels predict virological response to interferon-based therapy in Asian chronic hepatitis C patients. Antiviral therapy 10 23296193
2018 Increased Binding of Specificity Protein 1 to the IL21R Promoter in B Cells Results in Enhanced B Cell Responses in Rheumatoid Arthritis. Frontiers in immunology 6 30233580
2010 Development and application of a biomarker assay for determining the pharmacodynamic activity of an antagonist candidate biotherapeutic antibody to IL21R in whole blood. Journal of translational medicine 6 20509950
2021 WSB1 and IL21R Genetic Variants Are Involved in Th2 Immune Responses to Ascaris lumbricoides. Frontiers in immunology 4 33692795
2021 Combined immunodeficiency with marginal zone lymphoma due to a novel homozygous mutation in IL-21R gene and successful treatment with hematopoietic stem cell transplantation. Pediatric hematology and oncology 4 33966600
2024 IL21R hypomethylation as a biomarker for distinguishing benign and malignant breast tumours. Epigenetics 3 38723244
2023 ChIP-seq analysis found IL21R, a target gene of GTF2I-the susceptibility gene for primary biliary cholangitis in Chinese Han. Hepatology international 3 37713154
2025 Porphyromonas gingivalis Outer Membrane Vesicles Promote Gingival Fibroblasts Senescence via IL21R-AS1. Journal of periodontal research 2 40376960
2025 PTEN restricts IL-21R signaling in GC B cells and suppresses their differentiation to plasma cells. Journal of immunology (Baltimore, Md. : 1950) 2 40795247
2010 Assessing agonistic potential of a candidate therapeutic anti-IL21R antibody. Journal of translational medicine 2 20504348
2019 Short Communication: Nonprogressive HIV-1 Infection Is Associated with Expansion of IL-21R Expressing Class-Switched Memory B Cells. AIDS research and human retroviruses 1 31044603
2019 Corrigendum: Increased Binding of Specificity Protein 1 to the IL21R Promoter in B Cells Results in Enhanced B Cell Responses in Rheumatoid Arthritis. Frontiers in immunology 1 31156654
2025 [Corrigendum] IL‑21R functions as an oncogenic factor and is regulated by the lncRNA MALAT1/miR‑125a‑3p axis in gastric cancer. International journal of oncology 0 40747659
2025 IL17RA and IL21R polymorphisms influence type 1 diabetes predisposition and autoimmune phenotypes. Frontiers in endocrinology 0 40979706

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