Affinage

PTPN22

Tyrosine-protein phosphatase non-receptor type 22 · UniProt Q9Y2R2

Length
807 aa
Mass
91.7 kDa
Annotated
2026-06-10
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTPN22 (LYP/PEP) is a hematopoietic non-receptor protein tyrosine phosphatase that raises the activation threshold of immune cells by dephosphorylating activating tyrosines in antigen-receptor and Fc-receptor signaling cascades (PMID:16461343, PMID:36961507). In T cells it directly dephosphorylates the activating sites on Lck (Tyr-394) and ZAP70 (Tyr-493) while sparing their inhibitory tyrosines, and it acts on TCRzeta, Vav, and CD3epsilon, thereby attenuating proximal TCR signaling (PMID:16461343). It also targets the microtubule end-binding protein EB1 at Tyr-247 through its P1 domain, dampening downstream ZAP-70/LAT/Erk activation, NFAT, and IL-2 output (PMID:32469452). Its inhibitory action depends on recruitment to the plasma membrane and on association with CSK; PKCalpha-mediated Ser751 phosphorylation stabilizes PTPN22 against K48-ubiquitin-driven degradation while impairing membrane recruitment and enhancing CSK binding, and TRAF3 likewise restrains membrane localization to permit T cell activation (PMID:32184287, PMID:28522807). PTPN22 catalytic activity is redox-controlled through a non-catalytic Cys129–catalytic Cys227 disulfide that, when disrupted, sensitizes the enzyme to NOX2/Ncf1-derived oxidation and heightens TCR-driven autoimmunity (PMID:35587260). Beyond T cells, PTPN22 governs innate immune responses: it promotes TLR-induced type I interferon by facilitating K63-linked TRAF3 ubiquitination, restrains NLRP3 inflammasome activation by promoting autophagy-dependent sequestration of phosphorylated NLRP3, suppresses M1 macrophage polarization, and negatively regulates FcgammaR- and dectin-1-driven neutrophil and dendritic-cell effector functions (PMID:23871208, PMID:28786745, PMID:23913970, PMID:27807193, PMID:28948613, PMID:30139951). It also expands regulatory T cells via GITR signaling and, outside immunity, dephosphorylates PDE5A in platelets to limit arterial thrombosis (PMID:26810223, PMID:35767715). The autoimmunity-associated R620W (mouse R619W) variant disrupts CSK binding and membrane-localized phosphatase function, fails to promote TRAF3 ubiquitination and type I IFN responses, and selectively lowers the signaling threshold of low-avidity self-reactive T cells, establishing it as a loss-of-function risk allele for autoimmunity (PMID:23871208, PMID:23619366, PMID:36961507).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2006 High

    Establishing PTPN22's direct substrates answered how it suppresses TCR signaling at the molecular level, showing selective removal of activating rather than inhibitory phosphotyrosines.

    Evidence substrate-trap mutagenesis with mass spectrometry, in vitro dephosphorylation of purified proteins, and co-IP in Jurkat/293T cells

    PMID:16461343

    Open questions at the time
    • Did not define which substrate dephosphorylation dominates in vivo
    • Membrane recruitment and spatial regulation not addressed
    • Disease-variant effect on catalysis not tested
  2. 2012 Medium

    Identification of the dominant-negative PTPN22.6 splice isoform revealed an additional layer of regulation and a mechanism by which the W620 variant context drives T cell hyperactivation.

    Evidence splice-variant identification and dominant-negative functional assays in human T cells

    PMID:22427951

    Open questions at the time
    • Physiological abundance of PTPN22.6 in primary cells unclear
    • Structural basis of dominant-negative action not resolved
  3. 2013 High

    Three studies extended PTPN22 beyond TCR inhibition, showing positive control of TLR-driven type I IFN via TRAF3 ubiquitination, in vivo autoimmunity in the R619W knockin, and suppression of M1 macrophage polarization.

    Evidence PTPN22-TRAF3 Co-IP and ubiquitination assays, knockin and KO mouse models with colitis/arthritis and macrophage phenotypes

    PMID:23619366 PMID:23871208 PMID:23913970

    Open questions at the time
    • Whether TRAF3 ubiquitination is catalytic or scaffolding by PTPN22 unresolved
    • Cell-type specificity of pro- vs anti-inflammatory roles not unified
    • Direct substrate driving M1/M2 skewing unidentified
  4. 2016 Medium

    A series of studies mapped PTPN22's roles across innate and adaptive compartments — FcgammaR-mediated neutrophil activation, GITR-dependent Treg expansion, ZAP70-context arthritis, and dual CD8 T cell regulation.

    Evidence Ptpn22-/- and knockdown mice with neutrophil functional assays, GITR-blockade rescue, SKG epistasis, and LCMV infection models

    PMID:26810223 PMID:27288531 PMID:27725666 PMID:27807193

    Open questions at the time
    • Direct phosphatase substrates in neutrophils, Tregs, and CD8 T cells not biochemically defined
    • Mechanism of positive IFN-alpha/STAT-1 regulation unresolved
    • Single-lab phenotypes
  5. 2017 Medium

    Work this year placed PTPN22 within innate inflammasome and pattern-recognition pathways, showing autophagy-dependent NLRP3 control, dectin-1/Syk regulation in DCs, and TRAF3-controlled membrane localization.

    Evidence KO macrophages with autophagy manipulation and NLRP3 fractionation, Ptpn22-R619W BMDC dectin-1 assays, TRAF3-deficient T cell membrane fractionation

    PMID:28522807 PMID:28786745 PMID:28948613

    Open questions at the time
    • Whether PTPN22 directly dephosphorylates NLRP3 not established
    • Kinase/phosphatase coupling to autophagy machinery unclear
    • Reciprocal validation limited to single labs
  6. 2018 Medium

    Studies defined PTPN22's negative control of antigen presentation and adhesion-driven Th1 responses, distinguishing T cell-intrinsic and DC-extrinsic mechanisms.

    Evidence Ptpn22-/- BMDC immune-complex presentation assays, planar bilayer immune synapse imaging, LFA-1 blockade and adoptive transfer

    PMID:30054208 PMID:30139951

    Open questions at the time
    • Molecular substrates governing synapse and LFA-1 signaling not identified
    • Relative contribution of intrinsic vs extrinsic effects in disease unquantified
  7. 2020 High

    Discovery of PKCalpha-driven Ser751 phosphorylation and EB1 as a substrate clarified how PTPN22's stability, membrane recruitment, CSK binding, and microtubule-linked signaling are coordinated.

    Evidence mass spectrometry phosphosite mapping, in vitro PKCalpha kinase and ubiquitination assays, fractionation, CSK Co-IP, yeast two-hybrid and EB1 dephosphorylation

    PMID:32184287 PMID:32469452

    Open questions at the time
    • How Ser751 phosphorylation mechanistically blocks membrane recruitment unresolved
    • Why R620W membrane recruitment is insensitive to Ser751 phosphorylation not explained
  8. 2022 High

    Three studies added redox regulation via the Cys129–Cys227 disulfide, a platelet PDE5A serine-phosphatase function, and TRAF3-gated PTPN22 recruitment to IFNAR, broadening PTPN22's activity and regulation.

    Evidence C129S knock-in mice with Ncf1 epistasis and thioredoxin assays, platelet KO thrombosis models with PDE5A Co-IP and purified-protein phosphatase assays, IFNAR Co-IP in TRAF3-deficient T cells

    PMID:35587260 PMID:35767715 PMID:36166512

    Open questions at the time
    • Physiological oxidant source for Cys129 oxidation beyond NOX2 unclear
    • Structural basis of intrinsic serine-phosphatase activity not defined
    • Generality of IFNAR recruitment across cell types untested
  9. 2023 High

    Isogenic CRISPR editing of R620W in primary human T cells established that the risk allele acts as a loss-of-function variant that selectively lowers the activation threshold of low-avidity self-reactive T cells.

    Evidence CRISPR/Cas9 knock-in/knockout in human cord blood T cells with patient-derived IGRP-specific TCRs and functional assays

    PMID:36961507

    Open questions at the time
    • In vivo relevance of low-avidity selectivity to human autoimmunity untested
    • Mechanism linking avidity threshold to PTPN22 substrate choice not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how PTPN22 mechanistically switches between negative regulation of antigen-receptor signaling and positive regulation of TRAF3/type I IFN pathways, and how its tyrosine- versus serine-phosphatase activities are partitioned across cell types.
  • No unified structural model integrating membrane recruitment, redox state, and substrate selection
  • Direct in vivo substrate repertoire in non-T cell lineages undefined
  • Mechanism of dual tyrosine/serine phosphatase activity not structurally explained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0016787 hydrolase activity 2
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-109582 Hemostasis 1
Partners
CSKEB1IFNARNLRP3PDE5ATRAF3

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 PTPN22 (LYP) dephosphorylates Lck at its activating tyrosine Tyr-394 and Zap70 at Tyr-493 (activating residues), but not at regulatory tyrosines Tyr-505 (Lck) or Tyr-319 (Zap70). TCRzeta was also identified as a direct substrate: native PTPN22 dephosphorylated TCRzeta in vitro and in cells, and a substrate-trap mutant (D195A/C227S) co-immunoprecipitated with TCRzeta. Additional novel substrates identified by substrate trapping coupled with mass spectrometry included Vav, CD3epsilon, and valosin-containing protein. Substrate trapping (PTPN22-D195A/C227S mutant) coupled with mass spectrometry in pervanadate-stimulated Jurkat cells; in vitro dephosphorylation assays with purified recombinant proteins; co-immunoprecipitation in 293T cells The Journal of biological chemistry High 16461343
2013 PTPN22 selectively promotes TLR-induced type I interferon (IFN) production in myeloid cells by directly associating with TRAF3 and promoting TRAF3 lysine-63-linked ubiquitination. The disease-associated PTPN22-W620 variant failed to promote TRAF3 ubiquitination and type I IFN upregulation. Co-immunoprecipitation (PTPN22–TRAF3 interaction); ubiquitination assays; Ptpn22-deficient mouse models; TLR stimulation of myeloid cells; in vivo colitis and arthritis models Immunity High 23871208
2013 The PEP-R619W knockin mouse (ortholog of human LYP-R620W) shows normal protein stability but hyperresponsive lymphocytes upon antigen-receptor engagement, with a distinct profile of tyrosine-phosphorylated substrates. Aged knockin mice develop effector T cell expansion, B cell expansion (transitional, germinal center, age-related), autoantibodies, and systemic autoimmunity. B lineage-restricted variant expression is sufficient to promote autoimmunity. Knockin mouse generation; lymphocyte activation assays; phosphoproteomic profiling; flow cytometry of lymphocyte subsets; autoantibody detection The Journal of clinical investigation High 23619366
2013 PTPN22 suppresses M1 macrophage polarization and reciprocally promotes M2-associated gene expression. PTPN22-deficient mice develop severe DSS-induced colitis with intestinal macrophages expressing higher M1 and lower M2 genes. An autoinhibition mechanism was identified whereby PTPN22 suppresses its own expression in M1 but not M2 macrophages. PTPN22-deficient mice; DSS colitis model; macrophage polarization assays; gene expression analysis; human macrophage genotype-expression correlation Journal of immunology Medium 23913970
2012 An alternative splice isoform of PTPN22, PTPN22.6, lacks nearly the entire phosphatase domain and functions as a dominant-negative isoform of full-length PTPN22. Expression of the W620 variant of PTPN22.6 (but not PTPN22.1-W620) leads to hyperactivation of human T cells. Identification of splice variant; dominant-negative functional assays in human T cells; comparison of full-length vs. splice isoform activity PloS one Medium 22427951
2017 Loss of PTPN22 results in decreased NLRP3 inflammasome activation via enhanced NLRP3 phosphorylation, and this inhibitory effect is dependent on autophagy: phosphorylated NLRP3 is sequestered into autophagosomes (phagophores), and loss of autophagy abolishes the inhibitory effect on NLRP3 activation observed upon loss of PTPN22. PTPN22 KO macrophages; autophagy inhibition; immunoprecipitation to detect NLRP3 in autophagosomes; NLRP3 phosphorylation assays; IL-1β secretion assays Autophagy Medium 28786745
2017 TRAF3 associates with PTPN22 and regulates its TCR/CD28-induced localization; loss of TRAF3 results in increased amounts of PTPN22 in T cell membrane fractions and decreased association of PTPN22 with CSK. TRAF3 thus promotes T cell activation partly by preventing membrane localization of PTPN22. Co-immunoprecipitation; membrane fractionation of TRAF3-deficient mouse and human T cells; phosphorylation assays for Lck Scientific reports Medium 28522807
2016 PTPN22 is a critical regulator of FcγR-mediated neutrophil activation: Ptpn22-/- neutrophils show reduced adhesion, reactive oxygen species production, and degranulation upon stimulation with immobilized immune complexes. Tyrosine phosphorylation of Lyn and Syk was altered in Ptpn22-/- neutrophils. Ptpn22-/- mice were protected from immune complex-mediated arthritis. Ptpn22-/- mice; neutrophil functional assays (ROS, degranulation, adhesion); phosphorylation analysis of Lyn and Syk; in vivo serum transfer arthritis model Journal of immunology Medium 27807193
2016 Ptpn22 knockdown in mice promotes Treg cell expansion by upregulating GITR and increasing GITR signaling, prolonging Treg survival (decreased apoptosis) rather than accelerating cell division. This expansion is dependent on GITR signaling, as GITR-ligand blockade prevented Treg expansion caused by Ptpn22 knockdown. Loss of Ptpn22 also increased the proportion of effector Tregs (CD44hiCD62Llo) at the expense of central Tregs. Ptpn22 siRNA knockdown in mice; GITR expression and signaling analysis; apoptosis assays; GITR-ligand blockade; flow cytometry of Treg subsets Journal of immunology Medium 26810223
2020 PTPN22 is phosphorylated at Ser751 by PKCα in Jurkat and primary human T cells upon activation. This phosphorylation prolongs PTPN22 half-life by inhibiting K48-linked ubiquitination, impairs its recruitment to the plasma membrane (necessary for inhibiting proximal TCR signaling), and enhances its interaction with CSK. The R620W variant retains Ser751 phosphorylation-dependent protection from degradation but its membrane recruitment is unaffected by Ser751 phosphorylation. Mass spectrometry identification of phosphorylation site; PKCα kinase assays; ubiquitination assays; plasma membrane fractionation; co-immunoprecipitation with CSK; phosphomimetic/non-phosphorylatable mutant analysis Science signaling High 32184287
2022 PTPN22 is expressed in both human and mouse platelets and negatively regulates platelet function and arterial thrombus formation. PTPN22 deficiency accelerates arterial thrombosis and enhances platelet aggregation, granule secretion, calcium mobilization, and clot retraction. Mechanistically, PTPN22 interacts with phosphorylated PDE5A (Ser92) and dephosphorylates it in activated platelets; reduced PDE5A phosphorylation is associated with increased cGMP signaling (vasodilator-stimulated phosphoprotein). Purified PTPN22, but not the catalytic mutant C227S, possesses intrinsic serine phosphatase activity. PTPN22-/- mice; tail-bleeding time; in vivo thrombosis models; quantitative phosphoproteomics; co-immunoprecipitation (PTPN22–PDE5A); in vitro phosphatase assay with purified proteins and C227S mutant; human platelet inhibition experiments Blood High 35767715
2020 PTPN22 interacts with EB1 (end-binding protein 1) via the P1 domain of PTPN22, competing with CSK for the same binding domain. The R620W variant does not affect EB1 association. PTPN22 dephosphorylates EB1 at tyrosine-247 (Y247), which decreases expression of T cell activation markers CD25 and CD69 and phosphorylation of ZAP-70, LAT, and Erk, leading to downregulation of NFAT and reduced IL-2 secretion. Yeast two-hybrid; mass spectrometry; co-immunoprecipitation; in vitro dephosphorylation assay; T cell activation assays with overexpression/knockdown constructs FASEB journal Medium 32469452
2022 PTPN22 activity is regulated by oxidation via the non-catalytic Cys129 residue, which forms a disulfide with catalytic Cys227. A C129S knock-in mouse showed stronger T cell-dependent inflammatory responses and autoimmune arthritis due to enhanced TCR signaling. The C129S mutant PTPN22 was more sensitive to oxidation and less amenable to reductive reactivation by the thioredoxin system. The pro-inflammatory effect of the C129S mutation was neutralized by a mutation in Ncf1 (a NOX2 complex component), establishing functional interaction between PTPN22 and Ncf1/NOX2-derived reactive oxygen species. C129S knock-in mouse; T cell activation and arthritis assays; in vitro oxidation/activity assays with purified proteins; genetic epistasis with Ncf1 mutation; thioredoxin reductase reactivation assay eLife High 35587260
2017 PTPN22 regulates dectin-1 signaling in dendritic cells by modulating Syk and Erk phosphorylation. Ptpn22-/- BMDCs activated by the dectin-1 agonist curdlan showed enhanced Syk and Erk phosphorylation, increased IL-1β secretion, and enhanced IL-17 T cell responses in an IL-1β-dependent manner. BMDCs expressing the Ptpn22-R619W variant (mouse ortholog of R620W) also showed increased IL-1β and IL-17 responses, indicating that in the dectin-1 context Ptpn22-R619W operates as a loss-of-function variant. Ptpn22-/- and Ptpn22-R619W knock-in BMDC; dectin-1 agonist stimulation; immunoblotting for Syk and Erk phosphorylation; in vitro and in vivo T cell co-culture assays; IL-1β neutralization European journal of immunology Medium 28948613
2018 PTPN22 negatively regulates FcγR-mediated antigen presentation in dendritic cells: Ptpn22-/- bone marrow-derived DCs pulsed with ovalbumin:anti-ovalbumin immune complexes have enhanced capability to present immune complex-derived antigens, induce T cell proliferation, and form DC-T cell conjugates. Ptpn22-/- BMDC; immune complex pulsing; DC-T cell co-culture with OT-II T cells; T cell proliferation assays; DC-T cell conjugate formation assays Scientific reports Medium 30139951
2018 PTPN22 negatively regulates LFA-1-dependent Th1 responses through two mechanisms: (1) a T cell-intrinsic mechanism whereby PTPN22 limits LFA-1/ICAM-1-dependent immune synapse formation and DC-T cell conjugate formation; (2) a T cell-extrinsic mechanism whereby PTPN22 in dendritic cells limits LFA-1-dependent Th1 induction by DCs. Ptpn22-/- mice; in vitro anti-CD3/LFA-1 stimulation vs. anti-CD3/anti-CD28 stimulation; planar lipid bilayer immune synapse assays; DC-T cell conjugate assays; adoptive transfer experiments; LFA-1 blockade Journal of autoimmunity Medium 30054208
2022 TRAF3 enhances type I IFN signaling in CD4+ T cells by preventing recruitment of PTPN22 to the IFNAR complex, thereby enabling activation of JAK1 and STAT1 downstream of IFNAR. Co-immunoprecipitation of PTPN22 with IFNAR complex; TRAF3-deficient T cells; JAK1 and STAT1 phosphorylation assays; CD4+ T cell differentiation assays Science signaling Medium 36166512
2016 Loss of PTPN22 in SKG mice (which carry a hypomorphic ZAP70 allele) reduces the severity of mannan-induced autoimmune arthritis. Ptpn22 deficiency biases CD4+ Th cell differentiation away from the pathogenic Th17 lineage toward a Th1/Treg-focused response, without significantly altering thymocyte development or repertoire selection. SKG Ptpn22-/- double-mutant mice; mannan-induced arthritis model; flow cytometry of T cell subsets; Th17/Th1/Treg differentiation assays Journal of immunology Medium 27288531
2023 CRISPR/Cas9 gene editing of PTPN22-R620W in primary human naive T cells shows that the risk variant (620W) enhances TCR signaling and activation markers following non-specific TCR engagement, phenocopying PTPN22 KO. Using patient-derived TCRs against the autoantigen IGRP, loss of PTPN22 function (KO or 620W) enhanced signaling specifically in T cells expressing a lower-avidity self-reactive TCR (but not high-avidity TCR), promoting enhanced proliferation and Th1 skewing. CRISPR/Cas9 gene editing with donor templates in human cord blood T cells; lentiviral TCR delivery; T cell activation assays; proliferation assays; cytokine profiling eLife High 36961507
2016 PTPN22 has dual roles in CD8+ T cell responses: it promotes antigen-driven CD8 T cell expansion during acute LCMV infection by positively regulating IFN-α/STAT-1 signaling in T cells (Ptpn22-/- CD8 T cells show reduced STAT-1 upregulation and reduced STAT-1 phosphorylation in response to IFN-α); conversely, it inhibits homeostatic-driven proliferation (Ptpn22-/- CD8 T cells show increased expansion in lymphopenic hosts). LCMV infection of Ptpn22-/- mice; adoptive transfer into lymphopenic hosts; STAT-1 phosphorylation assays in response to IFN-α; flow cytometry of CD8 T cell subsets Immunology and cell biology Medium 27725666

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Gene-gene and gene-environment interactions involving HLA-DRB1, PTPN22, and smoking in two subsets of rheumatoid arthritis. American journal of human genetics 333 17436241
2006 The PTPN22 C1858T functional polymorphism and autoimmune diseases--a meta-analysis. Rheumatology (Oxford, England) 265 16760194
2006 Role of PTPN22 in type 1 diabetes and other autoimmune diseases. Seminars in immunology 258 16697661
2006 Identification of substrates of human protein-tyrosine phosphatase PTPN22. The Journal of biological chemistry 212 16461343
2006 PTPN22: setting thresholds for autoimmunity. Seminars in immunology 191 16731003
2014 PTPN22: the archetypal non-HLA autoimmunity gene. Nature reviews. Rheumatology 184 25003765
2011 Why is PTPN22 a good candidate susceptibility gene for autoimmune disease? FEBS letters 179 21515266
2013 Tyrosine phosphatase PTPN22: multifunctional regulator of immune signaling, development, and disease. Annual review of immunology 177 24364806
2013 The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-driven, type 1 interferon-dependent immunity. Immunity 172 23871208
2013 A disease-associated PTPN22 variant promotes systemic autoimmunity in murine models. The Journal of clinical investigation 158 23619366
2007 Protein tyrosine phosphatase PTPN22 in human autoimmunity. Autoimmunity 128 17729039
2017 PTPN22 regulates NLRP3-mediated IL1B secretion in an autophagy-dependent manner. Autophagy 112 28786745
2005 PTPN22 C1858T polymorphism in Colombian patients with autoimmune diseases. Genes and immunity 109 16163373
2006 Haplotype analysis revealed no association between the PTPN22 gene and RA in a Japanese population. Rheumatology (Oxford, England) 89 16690758
2012 Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue. Genes and immunity 87 23076337
2007 PTPN22: its role in SLE and autoimmunity. Autoimmunity 85 18075792
2007 Linkage proof for PTPN22, a rheumatoid arthritis susceptibility gene and a human autoimmunity gene. Proceedings of the National Academy of Sciences of the United States of America 78 17237219
2008 Mutation screening of PTPN22: association of the 1858T-allele with Addison's disease. European journal of human genetics : EJHG 72 18301444
2010 Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis. Annals of the rheumatic diseases 70 21131644
2005 HLA , CTLA-4 and PTPN22 : the shared genetic master-key to autoimmunity? Expert reviews in molecular medicine 69 16229750
1993 Cloning and sequencing of the Saccharomyces cerevisiae gene LYP1 coding for a lysine-specific permease. Yeast (Chichester, England) 67 8368011
2015 Genetic Variations of PTPN2 and PTPN22: Role in the Pathogenesis of Type 1 Diabetes and Crohn's Disease. Frontiers in cellular and infection microbiology 62 26734582
2013 PTPN22 modulates macrophage polarization and susceptibility to dextran sulfate sodium-induced colitis. Journal of immunology (Baltimore, Md. : 1950) 61 23913970
2005 Pathways to gene identification in rheumatoid arthritis: PTPN22 and beyond. Immunological reviews 56 15790351
2021 The role of PTPN22 in the pathogenesis of autoimmune diseases: A comprehensive review. Seminars in arthritis and rheumatism 55 33866147
2012 The putative role of the C1858T polymorphism of protein tyrosine phosphatase PTPN22 gene in autoimmunity. Autoimmunity reviews 53 23261816
2007 PTPN22 R620W functional variant in type 1 diabetes and autoimmunity related traits. Diabetes 51 17259401
2013 Roles of the protein tyrosine phosphatase PTPN22 in immunity and autoimmunity. Clinical immunology (Orlando, Fla.) 48 24269925
2021 Systemic inhibition of PTPN22 augments anticancer immunity. The Journal of clinical investigation 47 34283806
2012 PTPN22 R620W polymorphism in the ANCA-associated vasculitides. Rheumatology (Oxford, England) 47 22237046
2019 The Contribution of PTPN22 to Rheumatic Disease. Arthritis & rheumatology (Hoboken, N.J.) 46 30507064
2020 Autoimmunity linked protein phosphatase PTPN22 as a target for cancer immunotherapy. Journal for immunotherapy of cancer 43 33127657
2018 Regulation of autoimmune and anti-tumour T-cell responses by PTPN22. Immunology 43 29512901
2013 Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis. Annals of the rheumatic diseases 43 23946333
2017 Identification of PTPN22, ST6GAL1 and JAZF1 as psoriasis risk genes demonstrates shared pathogenesis between psoriasis and diabetes. Experimental dermatology 42 28603863
2020 Autoimmunity-Related Risk Variants in PTPN22 and CTLA4 Are Associated With ME/CFS With Infectious Onset. Frontiers in immunology 40 32328064
2020 PTPN22 gene polymorphism and susceptibility to rheumatoid arthritis (RA): Updated systematic review and meta-analysis. The journal of gene medicine 40 32333475
2008 The tryptophan 620 allele of the lymphoid tyrosine phosphatase (PTPN22) gene predisposes to autoimmune Addison's disease. Clinical endocrinology 39 18710467
2021 Influence of PTPN22 Allotypes on Innate and Adaptive Immune Function in Health and Disease. Frontiers in immunology 36 33717184
2013 The role of PTPN22 in autoimmunity: learning from mice. Autoimmunity reviews 34 24189282
2012 PTPN22.6, a dominant negative isoform of PTPN22 and potential biomarker of rheumatoid arthritis. PloS one 34 22427951
2010 PTPN22, PDCD1 and CYP27B1 polymorphisms and susceptibility to type 1 diabetes in Polish patients. International journal of immunogenetics 32 20518841
2022 Protein tyrosine phosphatase PTPN22 negatively modulates platelet function and thrombus formation. Blood 31 35767715
2018 PTPN22 and CTLA-4 Polymorphisms Are Associated With Polyglandular Autoimmunity. The Journal of clinical endocrinology and metabolism 31 29409002
2019 Deletion of PTPN22 improves effector and memory CD8+ T cell responses to tumors. JCI insight 30 31335326
2017 TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22. Scientific reports 30 28522807
2016 Genetic Association of PTPN22 Polymorphisms with Autoimmune Hepatitis and Primary Biliary Cholangitis in Japan. Scientific reports 29 27406031
2016 PTPN22 Is a Critical Regulator of Fcγ Receptor-Mediated Neutrophil Activation. Journal of immunology (Baltimore, Md. : 1950) 29 27807193
2013 PTPN22 gene polymorphism (C1858T) is associated with susceptibility to type 1 diabetes: a meta-analysis of 19,495 cases and 25,341 controls. Annals of human genetics 27 23438410
2022 Genetic Polymorphism of PTPN22 in Autoimmune Diseases: A Comprehensive Review. Medicina (Kaunas, Lithuania) 25 36013501
2012 Association of Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) C1858T gene polymorphism with susceptibility to autoimmune thyroid diseases: a meta-analysis. Endocrine journal 25 22374238
2022 Exosomal circ-PTPN22 and circ-ADAMTS6 mark T cell exhaustion and neutrophil extracellular traps in Asian intrahepatic cholangiocarcinoma. Molecular therapy. Nucleic acids 24 36700045
2015 Association of PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with rheumatoid arthritis: A meta-analysis update. Immunobiology 24 25963842
2019 Type 1 diabetes linked PTPN22 gene polymorphism is associated with the frequency of circulating regulatory T cells. European journal of immunology 22 31808541
2017 The lysin motif-containing proteins, Lyp1, Lyk7 and LysMe3, play important roles in chitin perception and defense against Verticillium dahliae in cotton. BMC plant biology 22 28870172
2016 Ptpn22 Modifies Regulatory T Cell Homeostasis via GITR Upregulation. Journal of immunology (Baltimore, Md. : 1950) 22 26810223
2016 Loss of the Protein Tyrosine Phosphatase PTPN22 Reduces Mannan-Induced Autoimmune Arthritis in SKG Mice. Journal of immunology (Baltimore, Md. : 1950) 22 27288531
2013 Variants in PTPN22 and SMOC2 genes and the risk of thyroid disease in the Jordanian Arab population. Endocrine 22 23463390
2013 Association between the PTPN22 1858C/T gene polymorphism and tuberculosis resistance. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 22 23499775
2022 Redox regulation of PTPN22 affects the severity of T-cell-dependent autoimmune inflammation. eLife 21 35587260
2013 The PTPN22 C1858T polymorphism and rheumatoid arthritis: a meta-analysis. Rheumatology international 21 23370857
2013 PTPN22 in autoimmunity: different cell and different way. Immunity 21 23890067
2010 PTPN22 gene polymorphisms in autoimmune diseases with special reference to systemic lupus erythematosus disease susceptibility. Journal of postgraduate medicine 21 20739780
2023 PTPN22 R620W gene editing in T cells enhances low-avidity TCR responses. eLife 20 36961507
2022 PTPN22: structure, function, and developments in inhibitor discovery with applications for immunotherapy. Expert opinion on drug discovery 20 35637605
2007 PTPN22 gene polymorphism in Behçet's disease. Tissue antigens 20 17868256
2020 Membrane Lipid Requirements of the Lysine Transporter Lyp1 from Saccharomyces cerevisiae. Journal of molecular biology 19 32413406
2018 Protein tyrosine phosphatase PTPN22 regulates LFA-1 dependent Th1 responses. Journal of autoimmunity 19 30054208
2020 PTPN22 phosphorylation acts as a molecular rheostat for the inhibition of TCR signaling. Science signaling 18 32184287
2018 The potential of PTPN22 as a therapeutic target for rheumatoid arthritis. Expert opinion on therapeutic targets 18 30251905
2013 Associations of the PTPN22 and CTLA-4 genetic polymorphisms with Taiwanese ankylosing spondylitis. Rheumatology international 18 24212676
2021 Proautoimmune Allele of Tyrosine Phosphatase, PTPN22, Enhances Tumor Immunity. Journal of immunology (Baltimore, Md. : 1950) 17 34417261
2018 The protein tyrosine phosphatase PTPN22 negatively regulates presentation of immune complex derived antigens. Scientific reports 17 30139951
2017 Protein tyrosine phosphatase PTPN22 regulates IL-1β dependent Th17 responses by modulating dectin-1 signaling in mice. European journal of immunology 17 28948613
2016 Autoimmune Variant PTPN22 C1858T Is Associated With Impaired Responses to Influenza Vaccination. The Journal of infectious diseases 17 27034343
2012 Protein tyrosine phosphatases and type 1 diabetes: genetic and functional implications of PTPN2 and PTPN22. The review of diabetic studies : RDS 17 23804260
2011 The role of PTPN22 gene polymorphism in childhood immune thrombocytopenic purpura. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 17 21597364
2011 The association between the PTPN22 C1858T polymorphism and rheumatoid arthritis: a meta-analysis update. Molecular biology reports 17 21706348
2008 PTPN22 gene polymorphism in Takayasu's arteritis. Rheumatology (Oxford, England) 17 18375974
2006 Are other protein tyrosine phosphatases than PTPN22 associated with autoimmunity? Seminars in immunology 17 16678435
2020 PTPN22 interacts with EB1 to regulate T-cell receptor signaling. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 32469452
2016 CD28 and PTPN22 are associated with susceptibility to rheumatoid arthritis in Egyptians. Human immunology 16 27125674
2011 No association of PTPN22 R620W gene polymorphism with rheumatic heart disease and systemic lupus erythematosus. Molecular biology reports 16 21384170
2011 The association between the PTPN22 C1858T polymorphism and systemic sclerosis: a meta-analysis. Molecular biology reports 16 21688149
2014 PTPN22 1858C>T gene polymorphism in patients with SLE: association with serological and clinical results. Molecular biology reports 15 24985973
2013 Metaanalysis of the association of smoking and PTPN22 R620W genotype on autoantibody status and radiological erosions in rheumatoid arthritis. The Journal of rheumatology 15 23637320
2011 PTPN22 and myasthenia gravis: replication in an Italian population and meta-analysis of literature data. Neuromuscular disorders : NMD 15 22197427
2009 PTPN22/LYP 1858C>T gene polymorphism and susceptibility to endometriosis in a Polish population. Journal of reproductive immunology 15 19237203
2007 Expression of human PTPN22 alleles. Genes and immunity 15 17230194
2020 The Relationship between PTPN22 R620W Polymorphisms and the Susceptibility to Autoimmune Thyroid Diseases: An Updated Meta-analysis. Immunological investigations 14 33103521
2016 Protein tyrosine phosphatase PTPN22 has dual roles in promoting pathogen versus homeostatic-driven CD8 T-cell responses. Immunology and cell biology 14 27725666
2014 The effect of the autoimmunity-associated gene, PTPN22, on a BXSB-derived model of lupus. Clinical immunology (Orlando, Fla.) 14 25463433
2012 PTPN22 and CTLA-4 gene polymorphisms in resected thymomas and thymus for myasthenia gravis. Thoracic cancer 14 28920273
2014 PTPN22 R620W polymorphism and ANCA disease risk in white populations: a metaanalysis. The Journal of rheumatology 13 25448792
2010 PTPN22 gene regulates natural killer cell proliferation during in vitro expansion. Tissue antigens 13 20522204
2022 TRAF3 enhances type I interferon receptor signaling in T cells by modulating the phosphatase PTPN22. Science signaling 12 36166512
2020 rs2476601 in PTPN22 gene in rheumatoid arthritis and periodontitis-a possible interface? Journal of translational medicine 12 33059697
2018 Novel missense mutation in PTPN22 in a Chinese pedigree with Hashimoto's thyroiditis. BMC endocrine disorders 12 30384852
2017 NLRP1, PTPN22 and PADI4 gene polymorphisms and rheumatoid arthritis in ACPA-positive Singaporean Chinese. Rheumatology international 12 28653215
2017 PTPN22 and islet-specific autoimmunity: What have the mouse models taught us? World journal of diabetes 12 28751955

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