RNA sequencing of BM myeloid cells treated with AAV-IL-27/ctrl in vivo
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA945343 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23876086_1.fastq.gz | Fastqsanger.gz | |||
| SRR23876086_2.fastq.gz | Fastqsanger.gz | |||
| SRR23876087_1.fastq.gz | Fastqsanger.gz | |||
| SRR23876087_2.fastq.gz | Fastqsanger.gz | |||
| SRR23876088_1.fastq.gz | Fastqsanger.gz |
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Project description:Interleukin-27 (IL-27) is a pleiotropic cytokine that exhibits stimulatory/regulatory functions on multiple lineages of immune cells and has a potential to be used as a therapeutic for cancer. We have recently demonstrated that systemic delivery of IL-27 using adeno-associated virus (AAV-IL-27) exhibits potent inhibition of tumor growth in mouse models. In this work, we demonstrate that AAV-IL-27 treatment leads to significant expansion of CD11b+Gr1+ myeloid cells (MCs). AAV-IL-27-induced expansion of CD11b+Gr1+ cells is IL-27R-dependent, requires Stat3 signaling but is inhibited by Stat1 signaling. AAV-IL-27 treatment does not increase the self-renewal capacity of CD11b+Gr1+ cells but induces significant expansion of hematopoietic stem cells (HSCs) and granulocyte-monocyte progenitor (GMP) cells. IL-27-induced Ly6G+ MCs upregulate MHC class I/II molecules but are less immune suppressive in vitro, and their expansion does not promote, but rather inhibit tumor growth in vivo. In the tumor microenvironment, IL-27 gene therapy appears to promote Ly6G+ MCs to differentiate into MHC class I/IIhigh and F4/80high macrophages. Thus, IL-27 gene therapy induces expansion of CD11b+Gr1+ myeloid cells and promotes their differentiation into anti-tumor M1 macrophages in tumor microenvironment.Bone marrow myeloid cells of tumor-bearing C57BL/6 mice treated with AAV-IL-27/ctrl for 2 weeks were sepreated by MACS. Transcriptome profiling (RNA-seq) of these purified Ly6G+ cells (>95%) was completed by BGI. Changing in gene express profiling resulted by IL-27 was analyzed in this study.
2024-03-09 | GSE227476 | GEO
Project description:Splenic CD8+ T cells of C57BL/6 mice treated with AAV-IL-27/ctrl for a month were sepreated by MACS. Transcriptome profiling (RNA-seq) of these purified CD8+ T cells (>95%) was completed by BGI. Changing in gene express profiling resulted by IL-27 was analyzed in this study.
2022-02-01 | GSE195736 | GEO
Project description:RNA sequencing of splenic CD8+ T cells treated with AAV-IL-27/ctrl in vivo
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Project description:Interleukin-27 (IL-27) can partially reduce tumor growth in several animal models, including pros-tate cancer. We describe our findings on the effects of IL-27 gene delivery on prostate cancer cells and how sequential therapy with IL-18 enhances the efficacy of IL-27. We applied IL-27 and IL-18 deliv-ery with the goal of reducing prostate tumor growth, first in cell culture and then in an immunocom-petent mouse model. The combination of IL-27 followed by IL-18 (2718) successfully reduced can-cer cell viability, with significant effects found for a particular combination sequence. Interestingly, when we compared the 2718 combination with a single cytokine targeted to IL-6R via an oligo-peptide (27pepL) recently developed by our group, we observed similar efficacy. This efficacy was further enhanced when 27pepL was sequenced with IL-18 (27pepL18)
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Project description:The pleiotropic cytokine IL-27 is essential for the clearance of the persistent LCMV strain Clone 13, however the cellular sources of IL-27 during viral infection are incompletely mapped and their relative importance unknown. Here we utilised single-cell RNA-sequencing of splenocytes from IL27-p28-GFP mice infected with Clone 13 to quantify the temporal patterns of IL-27 p28 production. IL-27-p28-GFP+ and IL-27-p28-GFP- splenocytes were sorted at 4 timepoints during Clone 13 infection and analysed by 3' single-cell transcriptome sequencing. Dendritic cells were major producers of early IL-27 with macrophages and monocytes being the predominant IL-27 producers during acute and persistent phases of infection. Interestingly, we also identified activated B cells and plasma cells as a prominent subset of IL-27-producing splenocytes and through B-cell-specific deletion of IL-27-p28 demonstrated that B-cell derived IL-27 is essential for sustained function of CD4 T cells and eventual clearance of Clone 13.
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Project description:IL-27, a member of the IL-12- family of cytokines, has shown anti-tumor activity in several pre-clinical models due to anti-proliferative, anti-angiogenic and immune-enhancing effects. On the other hand, IL-27 demonstrated immune-regulatory activities and inhibition of auto-immunity in mouse models. Also, we reported that IL-27, similar to IFN-, induces the expression of IL-18BP, IDO and PD-L1 immune-regulatory molecules in human cancer cells. Here, a proteomic analysis reveals that IL-27 and IFN- display a broad overlap of functions on human ovarian cancer cells. Indeed, among 990 proteins modulated by either cytokine treatment in SKOV3 cells, 814 showed a concordant modulation by both cytokines, while a smaller number (176) were differentially modulated. The most up-regulated proteins were common to both IFN-γ and IL-27. In addition, functional analysis of IL-27- regulated protein networks highlighted pathways of interferon signaling and regulation, antigen presentation, protection from natural killer cell-mediated cytotoxicity, regulation of protein polyubiquitination and proteasome, aminoacid catabolism and regulation of viral protein levels.
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Project description:Foxp3 expressing regulatory T cells (Tregs) are the central regulator of immune homeostasis and tolerance. As it is believed that proper Treg function is compromised under inflammatory conditions, exploring a pathway that enhances Treg function is of great importance. In this study, we report that IL-27, an IL-12 family cytokine known to play both pro- and anti-inflammatory role in T cells, plays a pivotal role in Treg function to control T cell-induced colitis. Unlike WT Tregs capable of inhibiting colitogenic T cell expansion and inflammatory cytokine expression, IL-27R-deficient Tregs were unable to downregulate inflammatory T cell responses. Tregs stimulated with IL-27 expressed substantially enhanced suppressive function both in vitro and in vivo. IL-27 stimulation of Tregs induced expression of LAG3, a surface molecule implicated in negatively regulating immune responses. LAG3 expression in IL-27-stimulated Tregs was critical to mediate suppressive Treg function. Finally, human Tregs also displayed enhanced suppressive function and LAG3 expression in response to IL-27 stimulation. Taken together, our results highlight a novel function of the IL-27/LAG3 axis in Treg regulation of inflammatory responses in the intestine. FACS purified Foxp3+ Tregs were stimulated in the presence of media or IL-27 to compare IL-27 induced gene profiles. Four samples (media stimulated or IL-27-stimulated) were collected from four independent experiments. Genes altered by IL-27 treatment were compared to those of media stimulated Tregs.
2015-11-01 | E-GEOD-63455 | biostudies-arrayexpress
Project description:Foxp3 expressing regulatory T cells (Tregs) are the central regulator of immune homeostasis and tolerance. As it is believed that proper Treg function is compromised under inflammatory conditions, exploring a pathway that enhances Treg function is of great importance. In this study, we report that IL-27, an IL-12 family cytokine known to play both pro- and anti-inflammatory role in T cells, plays a pivotal role in Treg function to control T cell-induced colitis. Unlike WT Tregs capable of inhibiting colitogenic T cell expansion and inflammatory cytokine expression, IL-27R-deficient Tregs were unable to downregulate inflammatory T cell responses. Tregs stimulated with IL-27 expressed substantially enhanced suppressive function both in vitro and in vivo. IL-27 stimulation of Tregs induced expression of LAG3, a surface molecule implicated in negatively regulating immune responses. LAG3 expression in IL-27-stimulated Tregs was critical to mediate suppressive Treg function. Finally, human Tregs also displayed enhanced suppressive function and LAG3 expression in response to IL-27 stimulation. Taken together, our results highlight a novel function of the IL-27/LAG3 axis in Treg regulation of inflammatory responses in the intestine.
2015-11-01 | GSE63455 | GEO