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Sequential Exposure to Interleukin-21 and Interleukin-15 During Human Natural Killer Cell Expansion Optimizes Yield and Function

ABSTRACT: Sequential Exposure to Interleukin-21 and Interleukin-15 During Human Natural Killer Cell Expansion Optimizes Yield and Function

PROVIDER: PRJNA981161 | ENA |

REPOSITORIES: ENA

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Sequential Exposure to Interleukin-21 and Interleukin-15 During Human Natural Killer Cell Expansion Optimizes Yield and Function

Project description:NK cells are frequently expanded for the clinic using irradiated engineered K562 feeder cells expressing a core transgene set of membrane-bound mb IL-15 and/or mbIL-21 together with 41BBL. Prior comparisons of mbIL-15 to mbIL-21 for NK expansion lack comparisons of key attributes of the resulting NK cells including their high dimensional phenotype, polyfunctionality, the breadth and potency of cytotoxicity, cellular metabolism, and activity in xenograft tumor models. Moreover, despite multiple rounds of K562 stimulation, studies of sequential use of mbIL-15- and mbIL-21-based feeder cells are absent. We addressed these gaps and found that using mbIL-15 versus mbIL-21-based feeder cells drove distinct phenotypic and functional profiles. Feeder cells expressing mbIL-15 alone drove superior functionality by nearly all measures, while those expressing mbIL-21 alone drove superior yield. In combination, most attributes resembled those imparted by mbIL-21, whereas in sequence NK yield approximated that imparted by the first cytokine, and the phenotype, transcriptome, and function resembled that driven by the second cytokine highlighting the plasticity of NK cell differentiation. The sequence mbIL-21 followed by mbIL-15 was especially advantageous in achieving significant yields of highly functional NK cells that demonstrated equivalent in vivo activity to those expanded by mbIL-15 alone in 2 of 3 xenograft models. Our findings define the impact of mbIL-15 versus mbIL-21 during NK expansion and reveal a previously under appreciated tradeoff between NK yield and function for which sequential use of mbIL-21- followed by mbIL-15-based feeder cells may be the optimal approach in many settings.

2023-09-30 | GSE234384 | GEO

Lamina propria Interleukin 17 A aggravates natural killer T cells activation in autoimmune hepatitis

Project description:Lamina propria Interleukin 17 A aggravates natural killer T cells activation in autoimmune hepatitis

| PRJNA819379 | ENA

Coulibaly2019 - Interleukin-15 Signaling in HIF-1a Regulation in Natural Killer Cells

Project description:This is a mathematical model comprised of non-linear ordinary differential equations describing the dynamic relationship between hypoxia-inducible factor-1 alpha (HIF-1a) mRNA, HIF-1a protein, and interleukin-15-mediated upstream signalling events in natural killer cells from human blood. Regulatory expressions are also included for mammalian target of rapamycin (mTOR), nuclear factor-kappa beta, and signal transducer and activator of transcription 3 (STAT3).

2024-09-02 | BIOMD0000000867 | BioModels

Bos frontalis strain:High yield and low yield

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| PRJNA246763 | ENA

Golden goat fiber yield

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FloChIP's sequential chip data

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Expression profiling of Natural killer B cells

Project description:Investigation of global gene expression levels between B cells, Natural killer cells and Natural killer B cells Gene expression profiling using sorted B cells, Natural killer cells and Natural killer B cells from WT mouse spleen. Total RNA extracted from WT cells were quantified by the NanoDrop ND-1000 and RNA integrity was assessed by standard denaturing agarose gel electrophoresis. The sample preparation and microarray hybridization were performed based on the NimbleGenâs standard protocols.

2016-05-17 | E-GEOD-80063 | biostudies-arrayexpress

Endothelial Cell CD36 Optimizes Tissue Fatty Acid Uptake

Project description:Endothelial Cell CD36 Optimizes Tissue Fatty Acid Uptake

| PRJNA478230 | ENA

Antitumor immunity induced by antibody-based natural killer cell engager therapeutics armed with not-alpha IL-2 variant

Project description:We report here the design of new antibody-based natural killer cell engager therapeutics (ANKET), single tetraspecific molecules engaging the NK cell activating receptors NKp46 and CD16, the β chain of the interleukin-2 receptor (IL-2R) and a tumor-associated antigen (TAA).

2022-10-05 | GSE214378 | GEO

Lamina propria Interleukin 17 A aggravates natural killer T cells activation in autoimmune hepatitis

Project description:Autoimmune hepatitis is an interface hepatitis characterized by the progressive destruction of the liver parenchyma, the cause of which is still obscure. Interleukin (IL)-17A is a major driver of autoimmunity, which can be produced by innate immune cells against several intracellular pathogens. Here, we investigated the involvement of IL-17A in a mice model of immune-mediated hepatitis with the intestine exposed to Salmonella typhimurium. Our results showed more severe Concanavalin (Con) A-induced liver injury and gut microbiome dysbiosis when the mice were treated with a gavage of S. typhimurium. Then the Natural Killer (NK) T cells were over-activated by the accumulated IL-17A in the liver in the Con A and S. typhimurium administration group. IL-17A could activate NKT cells by inducing CD178 expression via IL-4/STAT6 signaling. Furthermore, via the portal tract, the laminae propria mucosal-associated invariant T (MAIT) cell-derived IL-17A could be the original driver of NKT cells’ over-activation in intragastric administration of S. typhimurium and Con A injection. In IL-17A deficient mice, Con A-induced liver injury and NKT cells activation was alleviated. However, when AAV-sh-mIL-17a was used to specifically knock down IL-17A in liver, it seemed that hepatic IL-17a knock down did not significantly influence the liver injury. Our results suggested that, under Con A-induction, laminae propria MAIT-derived IL-17A activated hepatic NKT, and this axis could be a therapeutic target in autoimmune liver disease.

2023-03-01 | GSE199311 | GEO

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