IL21 protein Proteins
- Known as:
- IL21 protein Proteins
- Catalog number:
- orb84796
- Product Quantity:
- 10
- Category:
- -
- Supplier:
- Biorb
- Gene target:
- IL21 protein Proteins
Related genes to: IL21 protein Proteins
- 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 protein Proteins
Related articles to: IL21 protein Proteins
- Pancreatic ductal adenocarcinoma (PDAC) is refractory to most therapies, including immunotherapies, for which reinvigoration of CD8 T cells through immune checkpoint blockade is insufficient to induce long-term, durable remissions. Direct KRAS inhibitors (KRASi) have shown clinical promise, although acquired resistance is common. We modeled KRASi response and relapse in mice and demonstrated that, unlike chemotherapy or combinations with checkpoint blockade, an interleukin (IL)-21 cytokine mimic (21h10) induced long-term, durable remissions. Its efficacy depends on T helper 1 (Th1)-polarized CD4 T cells, but not on CD8 T cells or tumor cell expression of major histocompatibility complex class I (MHC class I). Specifically, CD4 T cells primed by type 2 conventional dendritic cells (cDC2s) produce interferon γ (IFN-γ), which promotes macrophage-mediated phagocytosis of tumor cells. Ex vivo treatment of human PDAC specimens with 21h10 induces IFN-γ production by infiltrating T cells. Thus, IL-21-elicited CD4 T cells exert antitumor activity in mice and potentially in humans, converting transient responses to KRAS inhibition into durable remissions. - Source: PubMed
Publication date: 2026/09/23
Qiang LiHoffman Megan TChun Jung-HoParent BrendanHambitzer FelixPeprah FrankKureshi Courtney T SLim Birkley SChang EugenaWalsh Michael JTello Julissa GAtajanova TavusShin HojeongPerkins CoreyKureshi RakeebMolina-Aponte YanirisDougan James MZuo ChongBrais LaurenClancy Thomas ECleary James MHornick Jason LHuffman Brandon MMancias Joseph DMolina GeorgeFairweather MarkNowak Jonathan APerez Kimberly JRubinson Douglas ASlater Sarahvan Dams RitchellWang JipingWolpin Brian MWong Kwok-KinSingh HarshabadAguirre Andrew JBaker DavidDougan MichaelDougan Stephanie K - Aging is a major risk factor for atherosclerosis and is accompanied by profound changes in the immune system, including effector T cell expansion, senescent cell accumulation, and increased pro-inflammatory signaling. Rapamycin, a promising rejuvenation therapeutic that inhibits mTORC1 and modulates immune aging, was investigated for its potential to attenuate pro-atherogenic immune responses in aged atherosclerotic mice. 80- to 90-week-old male Ldlr mice with established atherosclerotic lesions were treated intraperitoneally with rapamycin or control triweekly for 8 weeks. Systemic and plaque immunity was assessed by flow cytometry or single-cell RNA-sequencing. Plaque morphology was evaluated by histology. Rapamycin treatment reduced plaque macrophage content (0.73 ± 0.07 × 10 μm) compared to control (ctrl: 0.95 ± 0.09 × 10 μm, p < 0.05) and decreased total T cell numbers in vascular and lymphoid tissues. This was accompanied by a shift from effector to central memory phenotypes, particularly within the CD8 compartment, and a relative enrichment of regulatory CD4 T cells (Tregs). Single-cell transcriptomics of aortic Tregs revealed increased expression of suppressive genes (Foxp3, Tgfb1) upon rapamycin. Rapamycin also reduced T follicular helper cells, IL-21 expression, germinal center B cells, plasma cells, and total and oxidation-specific epitope-specific immunoglobulin levels. Additionally, age-associated B cells were diminished in spleen and lymph nodes, reflecting a broader anti-inflammatory effect on B cell immunity. Finally, aortic leukocytes displayed profoundly reduced senescent enrichment scores. Rapamycin remodels the immune landscape in aged atherosclerotic mice, promoting regulatory lymphocyte subsets and suppressing antigen-driven and inflammatory immune responses. These findings highlight the potential of immune-targeted rejuvenation to mitigate age-related atherogenic inflammation. - Source: PubMed
de Mol Jillde Korte Daphne HDepuydt Marie A CSmit VirginiaKleijn Mireia N A Bernabévan Santbrink Peter JBinder Christoph JPorsch FlorentinaSchaftenaar Frank HFoks Amanda C - Elevated levels of the pro-inflammatory cytokine Interleukin 21 (IL-21) contribute to the progression of autoimmune and inflammatory diseases by binding to its receptor (IL-21R) and activating detrimental signaling pathways in immune cells. Consequently, we developed a recombinant decoy receptor protein designed to competitively inhibit IL-21 binding to its receptor. Using the extracellular domain of IL-21R as a scaffold, five key binding-site residues (33, 38, 70, 94, and 130) were mutated with OSPREY software. Computational analyses with GROMACS selected the Q33S, E38D, M70T, L94N, and M130S mutant for its superior structural stability and high binding affinity to IL-21, with binding energy calculations confirming that the mutant successfully maintains the high baseline binding affinity of the wild-type complex. The decoy receptor protein was subsequently expressed recombinantly in Rosetta-gami. More importantly, the analysis of secondary structure revealed that the protein retained its overall secondary structure after mutagenesis, with slight alterations in alpha-helical content. Finally, the calculation of the value using the SPR technique demonstrated that the mutant IL-21R exhibited a 1.4-fold increase in binding affinity compared to the wild-type receptor ( vs. for the wild-type), supporting its potential as a competitive IL-21R decoy receptor. Therefore, this decoy receptor could be considered an effective therapeutic agent for blocking IL21 and controlling or preventing the progression of autoimmune and inflammatory diseases. - Source: PubMed
Publication date: 2026/09/23
Vazifeshenas SaraHajihassan ZahraArab Seyed ShahriarNajafyar Ali - Cell motility, characterized by random walk and exploratory search movement, enables effector CD8+ T cells to search for sparse antigen-specific cancer targets within a tumor. This is of special relevance for treatment of solid cancers with adoptive T-cell receptor (TCR) T-cell therapy, where administered effector CD8+ T cells recognize specific MHC-I-presented antigens. Cell motility requires cytoskeleton remodeling to facilitate shape changes and movement. Herein, we show that increased mitochondrial Ca2+ levels are essential to reduce cytoskeleton stiffness of effector CD8+ T cells, leading to acquisition of a polarized shape and high motility. IL-21, but not IL-7 or IL-15, was able to raise mitochondrial Ca2+ levels in effector CD8+ T cells and increase their motility without affecting survival and proliferation. This increase in mitochondrial Ca2+ levels triggered by IL-21 was driven by sustaining mitochondrial membrane potential through mitochondrial STAT3, independently of its transcriptional activity. Enhanced motility of effector CD8+ T cells led to a superior killing efficacy of antigen-specific melanoma cells in vitro. Furthermore, enhanced mitochondrial Ca2+-mediated motility of adoptive TCR-specific effector CD8+ T cells resulted in a superior antitumor efficacy of this treatment against solid tumors in vivo. Thus, enhancing effector CD8+ T-cell motility is a promising strategy to boost efficacy of adoptive T-cell therapies against solid tumors. - Source: PubMed
Publication date: 2026/09/21
Hoen Rauhut MaureenAbdullahi FahiimaWalters JayPatel Hiten NStich DominikMarié Isabelle JWen HaitaoLevy David EJacot Jeffrey GJacobelli JordanValenca-Pereira FelipeRincon Mercedes - Cancer-associated fibroblasts (CAFs) have been recognized as key contributors to tumor progression. Chimeric antigen receptor (CAR) T-cell therapy targeting fibroblast activation protein (FAP), a marker of CAFs, has gained attention and is being evaluated in both preclinical and clinical studies. Cord blood (CB)-derived CAR natural killer (NK) cell therapy has shown efficacy in hematologic malignancies. In this study, we generated FAP-targeting CAR NK cells (FAP-CAR NK cells). CD3-depleted CB mononuclear cells were stimulated with irradiated K562 cells expressing 4-1BB ligand (tumor necrosis factor ligand superfamily member 9) and membrane-bound interleukin-15 and interleukin-21 to expand NK cells, into which FAP-CAR was introduced. FAP-CAR NK cells produced cytokines and exerted cytotoxic activity when co-cultured with FAP-transduced HT1080 cells and CAFs isolated from human lung cancer tissue. In a xenograft model established by intrathoracic co-injection of A549 lung cancer cells and luciferase-expressing CAFs, injection of FAP-CAR NK cells, but not control CD19-CAR NK cells, resulted in their robust expansion and persistence in vivo for 5 weeks. However, CAFs were not eliminated by FAP-CAR NK cells, although CAR NK cells were clearly detected in the tumors. The levels of cytotoxicity-associated molecules (such as granzymes) were higher in FAP-CAR NK cells persisting in the spleens of mice compared with those in pre-infusion FAP-CAR NK cells. These results indicate that FAP-CAR NK cells have the potential to respond specifically to the target antigen and expand robustly in vivo, although further optimization is required to maintain cytotoxic function for a prolonged duration in vivo. - Source: PubMed
Publication date: 2026/09/20
Hiroshima TakashiKimura ToruMaekawa MarikoNoguchi MayukoMatsui TakahiroIkeda ShunyaSuga MakikoNagata HidekiKimura KenjiFukui ErikoKanou TakashiOse NaokoMorii EiichiShintani YasushiHosen Naoki