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Trans-presentation of interleukin-15 by interleukin-15
- Nature
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. IL-15Rα is dispensable for spontaneous T1D in NOD mice, but shows variable requirement for the maintenance of autoreactive CD8 + T cells. We have shown previously that IL-15 plays a critical role .. (PDF) IL-15.IL-15R complex shedding following trans-presentation is .. By generating an uncleavable form of IL-15Rα, we found an unprecedented cytokine pathway in which the IL-15.IL-15Rα complex cleaved from presenting cells allows responding cells to internalize .. The role of Interleukin-15 in inflammation and immune responses to .. 2. IL-15 expression and regulation. Mature human IL-15 is a 14-15 kDa glycoprotein and a member of the four α-helix bundle family of cytokines [].In both humans and mice cellular IL-15 production appears to be under stringent control through regulation of transcription, translation, translocation, and intracellular trafficking [].A variety of cell types constitutively express IL-15 mRNA .. Therapeutic potential of interleukin-15 in cancer (Review). 3. Interleukin-15 and preclinical studies. IL-15 is a cytokine that stimulates proliferation, activation and expansion of NK cells, as well as T-cell proliferation and generation of cytotoxic T lymphocytes, and sustaining of long-lasting antitumor immunity (18,33,34).Under normal conditions, soluble IL-15 (sIL-15) is difficult to be found in vivo, mainly due to its short half-life and the .. Trans-Presentation of IL-15 by Intestinal Epithelial Cells Drives .. Trans-presentation of IL-15 by parenchymal cells has been shown to drive IL-15-mediated development of IELs ; however, the identity of the parenchymal cell type involved had yet to be determined
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. Because IECs have long been recognized as a source of IL-15 in the intestines and are adjacent to IELs, IECs were speculated to be a likely cell type trans-presenting IL-15 for IEL development.. Engineered IL-15/IL-15R α -expressing cellular vesicles promote T cell .
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. ALT-803, a complex of an interleukin (IL)-15 superagonist mutant and a dimeric IL-15 receptor αSu/Fc fusion protein, was found to exhibit significantly stronger in vivo biologic activity on NK .. Interleukin 15 Receptor - an overview | ScienceDirect Topics. Interleukin-15. The IL-15 receptor consists of the IL-2Rβ and γc subunits in association with a unique ligand-specific subunit, IL-15Rα, which is homologous to IL-2Rα. These receptor proteins contain protein-binding motifs termed "sushi domains.". In both human and mouse, the genes encoding receptors are linked.. Biomimetic nanovaccine-mediated multivalent IL-15 self . - Nature. Cytokine therapy, involving interleukin-15 (IL-15), is a promising strategy for cancer immunotherapy. However, clinical application has been limited due to severe toxicity and the relatively low .. Reversible DNA Hypermethylation of the Interleukin-15 (IL-15) Promoter .. Reversible DNA Hypermethylation of the Interleukin-15 (IL-15) Promoter Induces IL-15 Expression, Drives the Pathogenesis of T-Cell Large Granular Lymphocytic Leukemia and Provides a Potential Therapeutic Approach Using 5-Azacitidine | Blood | American Society of Hematology. IL-15 in the Combination Immunotherapy of Cancer - PMC. Clinical Trials Using IL-15 in the Treatment of Cancer. We initiated a first-in-human phase I trial of recombinant Escherichia coli produced IL-15 administered by IV bolus daily for 12 days to patients with metastatic malignancy (2, 43) (Table 1).The initial dose of 3 μg/kg/day was too toxic with patients developing grade 3 thrombocytopenia and hypotension, and doses of 1.0 and 0.3 μg/kg/day .. Differential expression of interleukin‐15, a pro‐inflammatory cytokine .. Abstract Background Pro-inflammatory interleukin (IL)-15 plays a major role in host defense and chronic inflammation by stimulating T-lymphocyte recruitment and growth. Expression of IL-15 and IL-1. Skip to Article Content; Skip to Article Information; Search within. Search term
Advanced Search Citation Search. Search term. Advanced Search .. Engineered IL-15/IL-15Rα-expressing cellular vesicles promote T cell .. Interleukin 15 (IL-15) is a pivotal immune cytokine that responses to cancer stress signals and maintains tissue-resident memory T ( T RM) cells. It is therefore considered as a potent therapeutic immunomodulator agonist cancer.. Superagonist IL-15-Armed Oncolytic Virus Elicits Potent Antitumor .
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. Oncolytic immunotherapy is a promising novel therapeutic for cancer, and further preclinical studies may maximize its therapeutic efficacy. In this study, we construct a novel oncolytic vaccinia virus (VV) expressing a superagoinst IL-15, a fusion protein of IL-15 and IL-15Ralpha. This virus, named vvDD-IL15-Rα, possesses similar replication efficiency as the parental virus vvDD yet leads to .. Bench-to-bedside translation of interleukin-15 for immunotherapy .. IL-15 is a pleiotropic cytokine that stimulates the differentiation and proliferation of NK cells and T cells [6 -11]. IL-15 signals through a heterotrimeric receptor including the common gamma chain (γc) shared with IL-2, IL-4, IL-7, IL-9, and IL-21, the β chain shared with IL-2, and a unique IL-15R chain.. IL-15/IL-15 receptor biology: a guided tour through an expanding .
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. The cytokine interleukin-15 (IL-15) has a key role in promoting survival, proliferation and activation of natural killer (NK) and CD8+ T cells. Despite its functional similarities to IL-2, IL-15 affects a wider range of target cell populations and utilizes different mechanisms of signaling
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. Here, we …. Interleukin-15 enhances cellular proliferation and upregulates CNS .. The IL-15-mediated growth advantage is abolished by mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK), PI3K, and NF-κB inhibitors but preserved in the presence of STAT5 inhibition.. Xencor and Genentech partner on novel IL-15 cytokine drugs. Xencor will receive $120m upfront from Genentech, as well as being eligible to receive up to $160m in development milestones for XmAB2403 and $180m for other IL-15 products. XmAB2403 was engineered using Xencors bispecific Fc domain and Xtend Fc tech
Combining IL-15 with IL-15Rα means the drug binds to IL-15Rß to stimulate the expansion .. Rationale for IL-15 superagonists in cancer immunotherapy. 1. Introduction. Interleukin (IL)-15 (IL-15) is a promising cytokine for the treatment of hematological and solid malignancies. It is a member of the common receptor gamma chain (γ c) family, which also includes IL-2, IL-4, IL-7, IL-9, and IL-21. This group of cytokines has broad pleiotropic activity on both the innate and adaptive immune .. The emerging role of IL-15 in NK-cell development - Cell Press
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. Abstract. Natural killer (NK) and T cells appear to have a common progenitor cell. Interleukin 15 (IL-15) plays an important role in directing such progenitors to commit to NK-cell differentiation
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. Several other cytokines such as Flt-3 ligand and IL-7 appear to modulate or enhance the effects of IL-15.
IL-15 functions as a danger signal to regulate tissue-resident T cells .. This Opinion article proposes that interleukin-15 (IL-15) is a master regulator of tissue-specific T cell responses to promote the destruction of infected cells. Hence, dysregulation of IL-15 .
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. Interleukin-15 enhances cellular proliferation and upregulates CNS .. The IL-15 gene is expressed in many tissues, including the CNS. 21,22 Two IL-15 isoforms encode the same mature IL-15 protein but with different signal peptides determining cellular localization. 23 The 21-amino-acid short-signal peptide isoform (SSP-IL-15) is targeted to the cytoplasm; its function remains largely unknown. In contrast, the 48-amino-acid long-signal peptide isoform (LSP-IL-15 .. Membrane-bound and soluble IL-15/IL-15Rα complexes display differential .. To confirm the existence and the composition of the IL-15/IL-15R association, we performed coimmunoprecipitation experiments with an anti-IL-15 mAb on plasma-membrane fraction (Figure 2A) using mild detergent lysis conditions (digitonin).The membrane was subsequently reprobed by Western blotting with anti-IL-15Rα, β, γc, or anti-IL-15 Abs: a single 56-kDa specific band was detected by an .
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. Antibody blockade of IL-15 signaling has the potential to durably .. Targeting IL-15 signaling with an anti-CD122 antibody reverses disease in mice with established vitiligo. Short-term treatment with anti- CD122 inhibits TRM production of interferon- (IFN ), and long-term treatment depletes TRM from skin lesions. Short-term treatment with anti-CD122 can provide durable repigmentation when administered either .. Élection au Sénégal 2024: pourquoi le Conseil constitutionnel . - BBC
La très attendue décision est finalement tombée dans la soirée du jeudi 15 février. Le Conseil constitutionnel sénégalais a invalidé la décision de reporter lélection présidentielle du ..