RNA sequencing of splenic CD8+ T cells treated with AAV-IL-27/ctrl in vivo
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE195736 | GEO | 2022/02/01
REPOSITORIES: GEO
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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:RNA sequencing of splenic CD8+ T cells treated with AAV-IL-27/ctrl in vivo
| PRJNA802038 | ENA
Project description:RNA sequencing of BM myeloid cells treated with AAV-IL-27/ctrl in vivo
| PRJNA945343 | ENA
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.
2022-01-10 | GSE186898 | GEO
Project description:Viral vectors are attractive vaccine platforms that elicit robust innate and adaptive immune responses; however, viral vector vaccine candidates vary greatly in their ability to induce protective immunity. Ad5 vectors elicit robust CD8+ T cell responses but typically characterized by an exhausted phenotype. The mechanisms by which Ad5 vectors induce dysfunctional CD8+ T cells have not been fully elucidated. Here we demonstrate that Ad5 vectors, but not Ad26 vectors, elicit exhausted antigen-specific IL-10+PD1+ CD4+ T cells with a dysfunctional transcriptional profile, and these cells effectively suppress CD8+ T cells responses in vivo. Induction of inhibitory CD4+ T cells by Ad5 vectors was associated with increased IL-27 expression, and IL-27 blockade improved CD4+ T cell polyfunctionality. Together our data highlight a novel role for IL-27 in regulating responses to viral vector vaccines. Splenic CD45.2+ OT-II TCR-Tg CD4 T cells from CD45.1+ B6 mice immunized with Ad5-OVA or Ad26-OVA were purified by FACS on day 10 post-immunization
2016-06-01 | E-GEOD-73118 | biostudies-arrayexpress
Project description:Viral vectors are attractive vaccine platforms that elicit robust innate and adaptive immune responses; however, viral vector vaccine candidates vary greatly in their ability to induce protective immunity. Ad5 vectors elicit robust CD8+ T cell responses but typically characterized by an exhausted phenotype. The mechanisms by which Ad5 vectors induce dysfunctional CD8+ T cells have not been fully elucidated. Here we demonstrate that Ad5 vectors, but not Ad26 vectors, elicit exhausted antigen-specific IL-10+PD1+ CD4+ T cells with a dysfunctional transcriptional profile, and these cells effectively suppress CD8+ T cells responses in vivo. Induction of inhibitory CD4+ T cells by Ad5 vectors was associated with increased IL-27 expression, and IL-27 blockade improved CD4+ T cell polyfunctionality. Together our data highlight a novel role for IL-27 in regulating responses to viral vector vaccines.
2016-06-01 | GSE73118 | GEO
Project description:Chronic infection and cancer are associated with suppressed T cell responses in the presence of activating antigen. Recent work identified memory-like CD8+ T cells termed follicular cytotoxic T cells (TFC) which sustain T cell responses during persistent infection and are essential for the T-cell proliferative burst following PD1 blockade. Approaches to expand these cells are sought. We show that blockade of interferon type 1 (IFN-I) receptor leads to TFC expansion in an IL-27-and STAT1-dependent manner. IFNAR1 blockade promoted accelerated cell division and retention of TCF1 in virus-specific CD8+ T cells. We found that CD8+ T cell-intrinsic IL-27 signaling safeguards the ability of TCF1-high cells to sustain proliferation and prevents premature cell cycle exit and programmed cell death. Transcriptome analysis revealed an IL-27-regulated gene module controlling survival of activated CD8+ T cells which is enhanced in IFNAR-attenuated conditions. We further demonstrated a cell-intrinsic requirement for the IL-27 target IRF1 in TFC expansion through promoting sustained division. These findings reveal that IL-27 opposes IFN-I to uncouple cell division from effector differentiation, and suggest IL-27 signaling could be exploited to augment self-renewing T cell populations in patients with chronic infections.
2019-04-01 | GSE97139 | GEO
Project description:To examine the broad impact of IL-27 on human T lymphocytes, we performed a microarray analysis assessing >20,000 well annotated genes on purified naïve (CD45RA+CD45RO-CCR7+) and central memory (CD45RA-CD45RO+CCR7+) CD4+ and CD8+ T cells from three healthy donors that were activated in vitro (plate bound anti-CD3 and soluble anti-CD28) in the presence or absence of human recombinant IL-27 (100 ng/mL). Our goal was to investigate the impact of interleukin-27 on the gene expression profil of human CD4 and CD8 T lymphocytes.
2021-03-10 | GSE145334 | GEO
Project description:HIV-specific T cells have diminished effector function and fail to control/eliminate the virus. IL-27, a member of the IL-6/IL-12 cytokine superfamily has been shown to inhibit HIV replication however whether IL-27 can enhance function on HIV-specific T cell is largely unknown. Because of the important implication in cure strategies, in the present manuscript, we investigated the role of IL-27 signaling in human T cells by evaluating the global transcriptional changes and its impact in the function of HIV-specific T cells. We found that T cells from people living with HIV (PLWH), expressed higher levels of STAT1 that leads to enhanced STAT1 activation upon IL-27 stimulation. IL-27 induced transcriptional changes associated with IFN/STAT1-dependent pathways in CD4 and CD8 T cells. More importantly, IL-27 promoted cytokine secretion of TIGIT+HIVGag-specific T cell function by modulating the expression levels of T-bet. This new immunomodulatory property of IL-27 on HIV-specific T cell function suggests its potential therapeutic use in cure strategies.
2021-12-09 | GSE189997 | GEO
Project description:To dissect the molecular regulatory mechanism of Pbx1 in peripheral B cell survival and proliferation, splenic B cells from CKO and Ctrl mice were sorted and stimulated with anti-IgM for 6 hours. Then RNA was extracted for sequencing.
2023-03-24 | E-MTAB-12768 | biostudies-arrayexpress