Acute exercise mobilizes NKT-like cells with a cytotoxic transcriptomic profile but does not augment the potency of cytokine-induced killer (CIK) cells
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ABSTRACT:
PROVIDER: PRJNA877120 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21437900_1.fastq.gz | Fastqsanger.gz | |||
| SRR21437900_2.fastq.gz | Fastqsanger.gz | |||
| SRR21437869_1.fastq.gz | Fastqsanger.gz | |||
| SRR21437869_2.fastq.gz | Fastqsanger.gz | |||
| SRR21437870_1.fastq.gz | Fastqsanger.gz |
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Project description:CD3+/CD56+ Natural killer (NK) cell-like T-cells (NKT-like cells) represent <5% of blood lymphocytes, display a cytotoxic phenotype, and can kill various cancers. NKT-like cells can be expanded ex vivo into cytokine-induced killer (CIK) cells, however this therapeutic cell product has had mixed results against hematological malignancies in clinical trials. The aim of this study was to determine if NKT-like cells mobilized during acute cycling exercise could be used to generate more potent anti-tumor CIK cells from healthy donors. An acute exercise bout increased NKT-like cell numbers in blood 2-fold. Single cell RNA sequencing revealed that exercise mobilized NKT-like cells have an upregulation of genes and transcriptomic programs associated with enhanced anti-tumor activity, including cytotoxicity, cytokine responsiveness, and migration. Exercise, however, did not augment the ex vivo expansion of CIK cells or alter their surface phenotypes after 21-days of culture. CIK cells expanded at rest, during exercise (at 60% and 80% VO2max) or after (1h post) were equally capable of killing leukemia, lymphoma, and multiple myeloma target cells with and without cytokine (IL-2) and antibody (OKT3) priming in vitro. We conclude that acute exercise in healthy donors mobilizes NKT-like cells with an upregulation of transcriptomic programs involved in anti-tumor activity, but does not augment the ex vivo expansion of CIK cells.
2022-09-12 | GSE212740 | GEO
Project description:CD3+/CD56+ Natural killer (NK) cell-like T-cells (NKT-like cells) represent <5% of blood lymphocytes, display a cytotoxic phenotype, and can kill various cancers. NKT-like cells can be expanded ex vivo into cytokine-induced killer (CIK) cells, however this therapeutic cell product has had mixed results against hematological malignancies in clinical trials. The aim of this study was to determine if NKT-like cells mobilized during acute cycling exercise could be used to generate more potent anti-tumor CIK cells from healthy donors. An acute exercise bout increased NKT-like cell numbers in blood 2-fold. Single cell RNA sequencing revealed that exercise mobilized NKT-like cells have an upregulation of genes and transcriptomic programs associated with enhanced anti-tumor activity, including cytotoxicity, cytokine responsiveness, and migration. Exercise, however, did not augment the ex vivo expansion of CIK cells or alter their surface phenotypes after 21-days of culture. CIK cells expanded at rest, during exercise (at 60% and 80% VO2max) or after (1h post) were equally capable of killing leukemia, lymphoma, and multiple myeloma target cells with and without cytokine (IL-2) and antibody (OKT3) priming in vitro. We conclude that acute exercise in healthy donors mobilizes NKT-like cells with an upregulation of transcriptomic programs involved in anti-tumor activity, but does not augment the ex vivo expansion of CIK cells.
| S-EPMC9519182 | biostudies-literature
Project description:Invariant Natural killer T (iNKT) cells are a separate lineage of T lymphocytes with innate effector functions. They express an invariant TCR specific for lipids presented by CD1d and their development and effector differentiation rely on a unique gene expression program. We asked whether this program includes microRNAs, small non-coding RNAs that regulate gene expression posttranscriptionally and play key role in the control of cellular differentiation programs. We identified a miRNA profile specific for iNKT cells, which exhibits features of activated/effector T lymphocytes. In this experiment we compared microRNAs of NKT cells versus those of conventional T lymphocytes, both extracted from wild type mouse thymus. To produce the populations we enriched mature thymocytes and then sorted NKT cells and conventional T cells (from one sorting we obtain one â??NKTâ?? sample and one â??Tâ?? sample). We performed the experiment in triplicate; the sample NKT 1 was sorted the same day of the sample T 1, NKT 2 with T 2, NKT 3 with T 3. We used a common reference approach for the 6 samples; as a common reference we produced RNA from total thymocytes, without the enrichment for mature cells and without the sorting; we pooled thymocytes derived from all the thymi used in the study. The aim of the experiment was to demonstrate that NKT cells have a microRNA profile different from that of conventional T cells.
2010-04-09 | E-GEOD-15925 | biostudies-arrayexpress
Project description:The transcription factor PLZF (promyelocytic leukemia zinc finger) is encoded by the BTB domain-containing 16 (Zbtb16) gene. Its repressor function regulates specific transcriptional programs. During the development of invariant natural killer T (NKT) cells, PLZF is expressed and directs their effector program but the detailed mechanisms underlying PLZF regulation of multi-stage NKT cell developmental program are not well understood. This study investigated the role of acetylation-induced PLZF activation on NKT cell development by analyzing mice expressing a mutant form of PLZF mimicking constitutive acetylation (PLZFON mice). NKT populations in PLZFON mice were reduced in proportion and numbers of cells, and the cells present were blocked at the transition from developmental stage 1 to stage 2. NKT cell subset differentiation was also altered, with T-bet+ NKT1 and RORt+ NKT17 subsets dramatically reduced, and the emergence of a T-bet-RORt- NKT cell subset with features of cells in early developmental stages rather than mature NKT2 cells. Preliminary analysis of DNA methylation patterns suggested that activated PLZF acts on the DNA methylation signature to regulate NKT cells’ entry into the early stages of development, while repressing maturation. In wild-type NKT cells, deacetylation of PLZF is possible, allowing subsequent NKT cell differentiation. Interestingly, development of other innate lymphoid and myeloid cells, that are dependent on PLZF for their generation, is not altered in PLZFON mice highlighting lineage specific regulation. Overall, we propose that specific epigenetic control of PLZF through acetylation levels is required to regulate normal NKT cell differentiation. Key points: Constitutive acetylation of PLZF (PLZFON) blocks NKT cell development. PLZFON might act on the DNA methylation signature to control gene expression. PLZF acetylation levels regulate normal NKT cell differentiation.
2021-05-24 | GSE128558 | GEO
Project description:Semi-invariant natural killer T (NKT) cells are thymus-derived innate lymphocytes that modulate microbial and tumour immunity as well as autoimmune diseases. These immunoregulatory properties of NKT cells are acquired during their development. Much has been learnt regarding the molecular and cellular cues that promote NKT cell development, yet how these cells are maintained in the thymus and the periphery and how they acquire functional competence are incompletely understood. We found that IL-15 induced several Bcl-2 family survival factors in thymic and splenic NKT cells in vitro. Yet, IL15-mediated thymic and peripheral NKT cell survival critically depended on Bcl-xL expression. Additionally, IL-15 regulated thymic developmental stage 2 (ST2) to ST3 lineage progression and terminal NKT cell differentiation. Global gene expression analyses and validation revealed that IL-15 regulated Tbx21 (T-bet) expression in thymic ST3 NKT cells. The loss of IL15-dependent T-bet expression resulted in poor expression of IFN-γ and several NK cell receptors in NKT cells. Taken together, our findings reveal a critical role for IL-15 in NKT cell survival, which is mediated by Bcl-xL, and effector differentiation, which is regulated by T-bet. Gene expression was measured in NKT cells sorted from pooled thymi of wild-type (3 replicates) or IL-15 deficient (2 replicates) mice.
2011-12-08 | E-GEOD-32568 | biostudies-arrayexpress
Project description:The transcription factor PLZF (promyelocytic leukemia zinc finger) is encoded by the BTB 42 domain-containing 16 (Zbtb16) gene. Its repressor function regulates specific transcriptional 43 programs. During the development of invariant natural killer T (NKT) cells, PLZF is 44 expressed and directs their effector program but the detailed mechanisms underlying PLZF 45 regulation of multi-stage NKT cell developmental program are not well understood. This 46 study investigated the role of acetylation-induced PLZF activation on NKT cell development 47 by analyzing mice expressing a mutant form of PLZF mimicking constitutive acetylation (PLZFON mice). NKT populations in PLZFON 48 mice were reduced in proportion and numbers 49 of cells, and the cells present were blocked at the transition from developmental stage 1 to stage 2. NKT cell subset differentiation was also altered, with T-bet+ NKT1 and RORJt + 50 NKT17 subsets dramatically reduced, and the emergence of a T-bet - RORJt - 51 NKT cell subset 52 with features of cells in early developmental stages rather than mature NKT2 cells. Analysis 53 of DNA methylation patterns indicated that activated PLZF establishes a unique DNA 54 methylation signature to regulate NKT cells’ entry into the early stages of development, while 55 repressing maturation. In wild-type NKT cells, deacetylation of PLZF alleviates this 56 repression and allows subsequent NKT cell differentiation. Interestingly, development of 57 other innate lymphoid and myeloid cells, that are dependent on PLZF for their generation, is not altered in PLZFON 58 mice highlighting lineage specific regulation. Overall, we propose that 59 specific epigenetic control of PLZF through acetylation levels is required to regulate normal 60 NKT cell differentiation.
2021-04-21 | GSE171984 | GEO
Project description:Analysis of DOCK8 deficient animals revealed a novel marker of NKT cell development, the integrin CD103. The role of CD103 was further investigated by RNA microarray comparing CD103 negative versus positive NKT cells. Total RNA was extracted from 3 biological replicates of thymic, CD103positive NKT cells and compared using an Illumina microarray to CD103negative NKT cells.
2013-09-01 | E-GEOD-44815 | biostudies-arrayexpress
Project description:Natural killer (NKT) T cells exhibit tissue distribution, surface phenotype, and functional responses that are strikingly different from those of conventional T cells. The transcription factor PLZF is responsible for most of these properties, as its ectopic expression in conventional T cells is sufficient to confer to them an NKT-like phenotype. The molecular program downstream of PLZF, however, is largely unexplored. Here we report that PLZF regulates the expression of a surprisingly small set of genes, many with known immune functions. This includes several established components of the NKT cell developmental program. Transcriptional program downstream of PLZF in gammadelta NKT cells was analyzed by comparing wt, heterozygous and PLZF-deficient gammadelta NKT cells
2012-11-09 | E-GEOD-42168 | biostudies-arrayexpress
Project description:Type 1 NKT cells play a critical role in controlling the strength and character of adaptive and innate immune responses. Their functional characteristics are distinct from conventional T cells, and are induced by a transcriptional program initiated by positive selection on CD4+CD8+ (double positive, DP) thymocytes. Here we examined transcriptional events in four immature thymic NKT cell subsets in a novel Vα14 TCR transgenic strain bearing greatly expanded numbers of CD24+CD44- NKT cells. We used a transcriptional regulatory network approach to map TCR validation to the transition from DP T to DP NKT cells, and positive selection and lineage commitment to the transition from DP NKT to CD4 NKT
2021-12-15 | GSE106720 | GEO
Project description:Semi-invariant natural killer T (NKT) cells are thymus-derived innate lymphocytes that modulate microbial and tumour immunity as well as autoimmune diseases. These immunoregulatory properties of NKT cells are acquired during their development. Much has been learnt regarding the molecular and cellular cues that promote NKT cell development, yet how these cells are maintained in the thymus and the periphery and how they acquire functional competence are incompletely understood. We found that IL-15 induced several Bcl-2 family survival factors in thymic and splenic NKT cells in vitro. Yet, IL15-mediated thymic and peripheral NKT cell survival critically depended on Bcl-xL expression. Additionally, IL-15 regulated thymic developmental stage 2 (ST2) to ST3 lineage progression and terminal NKT cell differentiation. Global gene expression analyses and validation revealed that IL-15 regulated Tbx21 (T-bet) expression in thymic ST3 NKT cells. The loss of IL15-dependent T-bet expression resulted in poor expression of IFN-γ and several NK cell receptors in NKT cells. Taken together, our findings reveal a critical role for IL-15 in NKT cell survival, which is mediated by Bcl-xL, and effector differentiation, which is regulated by T-bet.
2011-12-08 | GSE32568 | GEO