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Whole proteome and phosphoproteome profiling of CD8+ and CD8- dendritic cells

ABSTRACT: Analyzing and comparing proteome and phosphoproteome profiling between CD8+ DC and CD8- DC not only will be very helpful to understand the molecular mechanisms regulating CD8+/- DC differentiation and function but also can screen CD8+ or CD8- DC specific regulatory pathways or molecules.

OTHER RELATED OMICS DATASETS IN: PRJNA392945

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Dendritic Cell

SUBMITTER: Yuxin Li

LAB HEAD: Junmin Peng

PROVIDER: PXD006875 | Pride | 2018-06-11

REPOSITORIES: Pride

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			Action	DRS
	pho1.3.pepXML	Pepxml
	pho1.raw	Raw
	pho2.3.pepXML	Pepxml
	pho2.raw	Raw
	pho3.3.pepXML	Pepxml

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Publications

Hippo/Mst signalling couples metabolic state and immune function of CD8α+ dendritic cells.

Du Xingrong X Wen Jing J Wang Yanyan Y Karmaus Peer W F PWF Khatamian Alireza A Tan Haiyan H Li Yuxin Y Guy Cliff C Nguyen Thanh-Long M TM Dhungana Yogesh Y Neale Geoffrey G Peng Junmin J Yu Jiyang J Chi Hongbo H

Nature 20180530 7708

Dendritic cells orchestrate the crosstalk between innate and adaptive immunity. CD8α+ dendritic cells present antigens to CD8+ T cells and elicit cytotoxic T cell responses to viruses, bacteria and tumours 1 . Although lineage-specific transcriptional regulators of CD8α+ dendritic cell development have been identified 2 , the molecular pathways that selectively orchestrate CD8α+ dendritic cell function remain elusive. Moreover, me ...[more]

PMID: 29849151

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Whole proteome and phosphoproteome profiling of J20 mice

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Whole proteome and phosphoproteome profiling of APPKI (NL-F) mice

Project description:Analyzing and comparing proteome and phosphoproteome profiling between WT and APPKI (NL-F) KI mice help us understand the molecular changes contributing to amyloid pathology development

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Whole proteome and phosphoproteome profiling of APPKI mice

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In vivo LPS responses in murine splenic CD8 and CD11b DC subsets

Project description:Background: Dendritic cells (DCs) are critical for regulating CD4 and CD8 T cell immunity, controlling Th1, Th2, and Th17 bias, generating inducible Tregs, and inducing tolerance. Multiple DC subsets have been identified in the mouse that are thought to have evolved to control these different immune outcomes. However, how these subsets differentially respond to inflammatory and/or tolerogenic signals in order to accomplish their divergent functionality remains unclear. Results: We analysed the responses of murine, splenic CD8 and CD11b DC subsets to in-vivo stimulation with lipopolysaccharide using RNA-Seq and systems biology approaches and observed responses are highly subset-specific. We reanalysed multiple datasets from the literature and show that these subset responses are obscured when analysing signaling at the population level. We show that the subset-specificity is due to the unique regulation of distinct TLR4 pathway modulators that ‘fine-tune’ a common TLR4 cascade rather and not due to major differences in signaling pathways or transcription factors. Conclusions: We propose the Pathway Modulation Model wherein common signaling pathways are regulated by unique sets of modulators allowing for distinct immune responses in closely related DC subsets. We extend these observations using analagous datasets from the literature and show that our model provides a global mechanism for generating cell subset-specific signaling in multiple subpopulations in mouse and man. Splenic CD8 and CD11b DC subsets from LPS stimulated (10 pooled animals) and Control (5 pooled animals) mice were analysed by RNA-Seq.

2014-07-01 | E-GEOD-42573 | biostudies-arrayexpress

Compartment resolved reference map from highly purified naive, activated, effector and memory CD8+ cells

Project description:Differentiation of CD8+ T lymphocytes into effector and memory cells is key for an adequate immune response and relies on complex interplay of pathways that convey signals from cell surface to nucleus. In this study, we fractionated four CD8+ T cell subtypes; naïve, recently activated effector, effector and memory cells into membrane, cytosol, soluble nucleus, chromatin-bound and cytoskeleton compartments. Using LC-MS/MS analysis, identified peptides were matched to human peptides/proteins (SwissProt). Compartment fractionation and gel-LC-MS separation identified 2399 proteins in total. Among these 735 were detected in all five, 241 in four, 257 in three, 368 in two and 798 found in only one fraction. Comparison between the two most different subsets, naïve and effector, yielded 146 significantly regulated proteins.

2015-02-04 | PXD001065 | Pride

Gene expression profiles of mouse splenic macrophages and CD8+ and CD8- conventional dendritic cells

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2011-06-17 | E-GEOD-30022 | biostudies-arrayexpress

Memory CD8+ T cells upregulate glycolysis and effector functions under limiting oxygen conditions

Project description:Memory CD8+ T cells are indispensable for maintaining long-term immunity against intracellular pathogens and tumors. Despite their presence in oxygen-deprived tissues of infection sites or tumors, the impact of local oxygen pressure on memory CD8+ T cells has remained largely unclear. We sought to elucidate how oxygen pressure impacted memory CD8+ T cells arising after infection with Listeria monocytogenes-OVA. Our data revealed that reduced oxygen pressure during in vitro culture switched CD8+ T cell metabolism from an OXPHOS to a glycolytic phenotype. Quantitative proteomic analysis showed that limiting oxygen conditions increased the expression of glucose transporters and components of the glycolytic pathway, while decreasing TCA cycle and mitochondrial respiratory chain proteins. The altered CD8+ T cell metabolism did not affect the expansion potential, but enhanced the granzyme B and IFN- production capacity. Memory CD8+ T cells cultured under low oxygen pressure were able to persist long-term in vivo and provided protection against bacterial rechallenge. Taken together, our study indicates that strategies of cellular immune therapy may benefit from reducing oxygen during culture to develop memory CD8+ T cells with superior effector functions .

2022-12-01 | PXD032236 | Pride

Murine CD8+ T cells: in vitro-derived vs. thymocytes

Project description:Transcriptional profiling of mouse in-vitro derived CD8+ cells (obtained after culturing BM-HSCs isolated from B6 mice) with OP9-DL1 cells for 35 days were compared to CD8+ thymocytes isolated from 4-5 weeks old B6 mice. Our goal was to determine similarities and differences in gene expression profile between in vitro-derived CD8+ cells and CD8+ cells isolated from the thymus. The procedure of in vitro differentiation of HSC using OP9-DL1 cocultures was previously described by: Schmitt, T. M., and J. C. Zuniga-Pflucker. 2002. Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro. Immunity 17:749-756 and Holmes, R., and J. C. Zuniga-Pflucker. 2009. The OP9-DL1 system: generation of T-lymphocytes from embryonic or hematopoietic stem cells in vitro. Cold Spring Harb Protoc 2009:pdb prot5156. Biological replicates: 2 different samples of in vitro-derived CD8+ T cells from day 35 were compared to 2 different samples of thymic CD8+ cells.

2012-09-05 | E-GEOD-37669 | biostudies-arrayexpress

Distinguishing innate memory CD8+ T from homeostatically expanded CD8+ T cells

Project description:Innate memory phenotype (IMP) CD8+ T cells are non-conventional αβ T cells exhibiting features of innate immune cells, and are significantly increased in the absence of non-receptor tyrosine kinase ITK. Their developmental path and function are not clear, particularly whether they can contribute to antigen specific responses. We found that WT bone marrow gives rise to IMP CD8+ T cells in irradiated MHCI-/- recipients, resembling those in Itk-/- mice determined by expression of surface markers. However, CD8+ T cells share similar expression of memory markers. We used microarrays to compare the global programme of gene expression to determine whether the CD8+ T cells selected by hematopoietic MHCI are IMP CD8+ T cells as observed in the absence of ITK, or the result of homeostatic expansion of T cell contamination in the donor bone marrow. Through analysis of global gene expression correlation and differential expression, we determined that hematopoietic MHCI dependent IMP CD8+ T cells generated in irradiated MHCI-/- recipients, resemble those in Itk-/- mice, but distinct from CD8+ T cells derived via homeostatic proliferation. Cell sorting was performed using a FACSAria Cell Sorter (BD Biosciences, San Diego, CA). IMP CD8+ T cells (TCRβ+CD8α+CD44hi) were sorted from splenocytes of WT→MHCI-/- chimeras 8 weeks post transplantation and 8-week old Itk-/- mice. To generate HP cells, naïve CD8+ T cells (TCRβ+CD8α+CD44lo) were sorted and injected into Rag1-/- recipients (0.5 million /mouse, retro-orbital injection), followed by sorting of TCRβ+CD8α+ splenocytes 8 weeks post adoptive transfer. We sought to compare cells with the same gender and age, thus all donors were female, and ages (absolute age for Itk null and age post transfer for chimeras and HP model) were 8 weeks.

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