IL21 Over_expression Lysate
- Known as:
- IL21 Over_expression Lysate
- Catalog number:
- LY10437a
- Product Quantity:
- 100ug
- Category:
- -
- Supplier:
- Abgen
- Gene target:
- IL21 Over_expression Lysate
Related genes to: IL21 Over_expression Lysate
- Gene:
- IL21 NIH gene
- Name:
- interleukin 21
- Previous symbol:
- -
- Synonyms:
- Za11, IL-21
- Chromosome:
- 4q27
- Locus Type:
- gene with protein product
- Date approved:
- 2000-03-29
- Date modifiied:
- 2019-04-23
Related products to: IL21 Over_expression Lysate
Related articles to: IL21 Over_expression Lysate
- Personalized neoantigen (neoAg) vaccines have shown clinical promise in solid tumors , yet their efficacy and mechanism of action in hematopoietic malignancies remain poorly defined . Herein, we establish an immunocompetent syngeneic A20 B-cell lymphoma platform to test the efficacy of neoAg vaccines used either as mono- or combinatorial therapies with other immunotherapies . Whereas subcutaneous A20 tumors were refractory to single-agent αPD-1 or αCTLA4 therapy, they were eradicated in a T cell-dependent manner in 90% of syngeneic hosts treated with dual immune checkpoint therapy (dual ICT, i.e., αPD-1 + αCTLA4). By mapping antigen specificity of dual-ICT-elicited T cells, we identified and validated dominant endogenous A20 MHC-I and MHC-II neoantigens and designed therapeutic synthetic long peptide (SLP) vaccines containing these neoepitopes. This vaccine (A20 neoVAX) promoted robust neoAg-specific CD4□ and CD8□ T cell responses in naïve syngeneic BALB/c mice and induced tumor rejection in ∼70% of subcutaneous tumor-bearing mice. In addition, nearly all mice rejected their subcutaneous A20 tumors when A20 neoVAX was combined with αPD-1. To render the results of this study more physiologic, we developed a systemic A20 lymphoma model and found that dual ICT failed to control tumor progression and A20 neoVAX delayed tumor progression and prolonged animal survival but did not induce tumor rejection. In contrast, A20 neoVAX plus dual ICT achieved durable systemic tumor elimination. Mechanistically, the combination of A20 neoVAX plus dual ICT amplified priming of A20 neoAg-specific T cells, prevented T cell dysfunction, sustained the cytotoxic capacity of tumor-specific CD8 T cells, and induced Th1-skewing of CD4 T cells in tumor and peripheral compartments. To increase the clinical relevance of these findings and to minimize potential adverse events in tumor-bearing, therapeutically treated individuals, we substituted CD8-targeted cytokine muteins (CD8-IL2 or CD8-IL21) for αCTLA4. These agents represent genetically modified forms of IL-2 or IL-21 that selectively stimulate CD8 T cells but have significantly reduced capacity to activate chronic inflammation and immunosuppressive functions of other immune cells. Whereas mice bearing systemic A20 lymphoma treated with either nothing, A20 neoVAX, or A20 neoVAX + CD8-IL2 failed to control tumor outgrowth, 66.7% of tumor-bearing mice treated with A20 neoVAX + CD8-IL2 + αPD-1 rejected their tumors. In similar experiments in which CD8-IL21 was substituted for CD8-IL2, tumor clearance was also observed in two-thirds of A20-bearing mice but now rejection occurred in the absence of αPD1. Together, these data define a framework for optimal personalized neoAg vaccination in B-lymphoma and demonstrate that neoAg vaccines can safely synergize with CD8 T cell-selective immunotherapies to prevent T-cell dysfunction and generate durable systemic anti-tumor immunity. - Source: PubMed
Publication date: 2026/08/06
Song YuangAladyeva EkaterinaVieira Medrano Ruan FTheisen Derek JArthur Cora DWhite J MichaelKohlmiller Heather BrinkVomund AnthonySinghal KartikHoang MyAmeh SamuelSheehan Kathleen C FLevy RonaldFehniger Todd AArtyomov Maxim NGriffith MalachiGriffith Obi LYeung Yik AndyDjuretic IvanaSultan HusseinSchreiber Robert D - Accumulating evidence demonstrates that the central nervous system (CNS) is not disconnected from the peripheral immune system; however, precisely how the adaptive immune system surveils the CNS remains a critical question. Recent findings reveal that channels between the skull and the dura mater facilitate the exchange of cerebrospinal fluid and immune cells between the CNS and skull bone marrow of mice under both homeostatic and disease conditions. Skull bone marrow functions as a source of immune cells for the CNS, yet its role in CNS antigen-specific adaptive immune responses remains unclear. Here we identify lymphoid structures within the skull bone marrow, featuring germinal-centre-like formations and containing a distinct population of follicular-helper-like T cells that promote B cell activation and humoral immunity through CD40L, IL-21 and IFNγ signalling. Adaptive immune cells within these skull bone marrow lymphoid structures surveil and respond to CNS-derived antigens and contribute to anti-tumour immune responses in mouse brain cancer models. Together, our findings show that the skull bone marrow is a site of CNS immunosurveillance that may influence immune responses across diverse neurological diseases. - Source: PubMed
Publication date: 2026/08/19
Park Jang HyunAbramishvili DavitiDavanzo Gustavo GastãoSilva RubenGu XingxingDu SilingLee Daniel DZinselmeyer Bernd HTurner Jackson SRandolph Gwendalyn JSmirnov IgorKipnis Jonathan - CD4+ T cell dysfunction plays a critical role in the pathogenesis of rheumatoid arthritis (RA). In this study, we investigated the expression, phenotypic characteristics, and potential clinical significance of CD55, a membrane-bound complement regulatory protein, in peripheral blood CD4+ T cells from RA patients. Flow cytometric analysis revealed that CD55 expression was highest in naive CD4+ T cells and was significantly reduced in patients with early RA compared with healthy controls. Functionally, CD55+CD4+ T cells displayed enhanced production of IL-17, IL-21, and IL-22 following stimulation and exhibited reduced susceptibility to complement deposition. Transcriptomic analysis identified distinct molecular signatures associated with CD55 expression, which were further validated at the protein level, including increased expression of PAX5, CR2, and CD248 in CD55+CD4+ T cells. In addition, CD55 expression was inversely associated with p38 MAPK activation, suggesting a link between CD55 downregulation and aberrant T cell activation. Receiver operating characteristic analysis demonstrated that CD55+CD4+ T cell frequency possessed diagnostic value for distinguishing patients with early RA from healthy controls and primary Sjögren's syndrome patients. Collectively, these findings identify CD55 as a marker of a distinct CD4+ T cell subset with altered functional and molecular characteristics and support its potential utility in the early diagnosis and differential diagnosis of RA. - Source: PubMed
Bahabayi AyibaotaGao YimingXiong ZiqiSun XiaochenLi QiZhang ZhonghuiWang GuochongLiu Chen - Common variable immunodeficiency (CVID) is frequently complicated by autoimmune and inflammatory manifestations associated with profound immune dysregulation (CVIDc), including expansion of T-betCD21 B cells (CD21 B cells). Elevated serum IL-10 levels have repeatedly been reported in CVIDc, yet their relationship to CD21 B-cell differentiation remains unclear. In this study, we determined a significant correlation between increased serum IL-10 levels and frequency of circulating CD21 B cells, particularly marked in CVIDc patients. Transcriptomic and protein analyses identified multiple cellular sources of IL-10 in CVID, including monocytes, T cells, and a subset of CD21 B cells in peripheral blood and inflamed tissues. CD21 B cells expressed elevated levels of IL-10 receptor subunits and displayed intact IL-10-induced STAT3 signaling, indicating preserved responsiveness to IL-10. Functionally, IL-10 alone neither induced CD21 B-cell differentiation nor inhibited IFN-γ-driven polarization. However, in vitro differentiation assays showed that IL-10 can substitute for IL-21 during CD40L/T cell-dependent differentiation of CD21-like B cells and promote their survival in vitro. These findings suggest that IL-10 may support the expansion and persistence of CD21 B cells at inflammatory sites. Collectively, our data identify IL-10 as a component of the inflammatory environment associated with CD21 B-cell expansion and suggest that IL-10 can functionally replace IL-21 during their differentiation and promote their survival in CVID-associated immune dysregulation. - Source: PubMed
Publication date: 2026/08/15
Cousin VictoriaGraumann AnnaGeiger ValerieSökler DavidBez PatrickGutenberger SylviaGlaser CorneliaAndrieux GeoffroyBoerries MelanieFrye Björn ChristianZissel GernotCalvillo Celia LourdesRodriguez-Ubreva JavierBallestar EstebanHauck FabianVoll Reinhard EChevalier NinaKeller BaerbelWarnatz Klaus - Anti-interferon-γ (IFN-γ) autoantibody (AAb)-associated adult-onset immunodeficiency (AOID) is an emerging disorder in East Asian adults characterized by severe opportunistic infections despite negative HIV status. The mechanisms driving anti-IFN-γ AAb production remain unclear. This study investigated B-cell gene expression, serum cytokine profiles, associations with AAb levels, and IFN-γ genetic variations in AOID patients. A cross-sectional study was conducted in 63 AOID patients and 30 healthy controls at Chiang Mai University Hospital, Thailand. Patients were classified as active or inactive according to infection status. B-cell gene expression, serum cytokines, anti-IFN-γ Aabs levels, and IFN-γ polymorphisms were analyzed by quantitative PCR, multiplex assays, ELISA, and nucleotide sequencing, respectively. AOID patients exhibited increased and expression and reduced , , , and expression. Active patients had higher levels of TNF-α, IL-6, IL-17A, IL-10, IL-21, and more chemokines than inactive patients. AAb levels positively correlated with TNF-α, IL-6, and IL-10. Correlation analysis showed positive associations among , , and , and a negative association between and . No significant IFN-γ sequence differences were identified within the analyzed transcript region. These findings suggest altered B-cell gene expression and inflammatory cytokine profiles in AOID, which may be associated with the immunological alterations observed in these patients and may provide insights into potential mechanisms underlying anti-IFN-γ AAb production. - Source: PubMed
Publication date: 2026/08/04
Rattanathammethee KritsadeeChawansuntati KriangkraiLumjuan NongkranNusartsang NattayaChaiwarith RomaneePraparattanapan JutaratSupparatpinyo KhuanchaiWipasa Jiraprapa