IL-27 mediates HLA class I up-regulation, which can be inhibited by the IL-6 pathway, in HLA-deficient Small Cell Lung Cancer cells

Carbotti, Grazia; Nikpoor, Amin Reza; Vacca, Paola; Gangemi, Rosaria; Giordano, Chiara; Campelli, Francesco; Ferrini, Silvano; Fabbi, Marina

doi:10.1186/s13046-017-0608-z

Cited by 20 publications

(20 citation statements)

References 52 publications

(78 reference statements)

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“…Primers and TaqMan probes for detecting IL-1α (assay Id, Hs00174092_m1), IL-6 (assay ID, Hs00985639_m1), IL-8 (assay ID, Hs00174103_m1), TNF-α (assay ID, Hs01113624_g1) and 18S ribosomal (r)RNA (assay ID, Hs03928990_g1) were supplied with the TaqMan Gene Expression Assay (Applied Biosystems; Thermo Fisher Scientific, Inc.). The relative gene expression was calculated via the ΔΔcq method (42)(43)(44)(45)(46). The ΔΔcq method uses the normalized Δcq value of each sample, which was calculated with 18S rRNA as the endogenous control gene.…”

Section: Liquid Chromatography Tandem Ms (Lc-ms/ms) Analysis For Protmentioning

confidence: 99%

Collagen peptides from soft‑shelled turtle induce calpain‑1 expression and regulate inflammatory cytokine expression in HaCaT human skin keratinocytes

et al. 2018

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Collagen peptides (CPs), derived by hydrolyzing collagen with chemicals or enzymes, are often used as functional materials, due to their various bioactivities and high bioavailability. A previous study by our group reported that collagen from soft‑shelled turtle, Pelodiscus sinensis, induces keratinocytes to undergo epithelial‑mesenchymal transition and facilitates wound healing. Therefore, CPs derived from soft‑shelled turtle collagen may have useful effects on the skin. In the present study, the functional effects of CPs on human skin were examined by analyzing CP‑treated human keratinocytes with a shotgun liquid chromatography/mass spectrometry‑based global proteomic approach. A semi‑quantitative method based on spectral counting was applied and 211 proteins that exhibited>2‑fold changes in expression after CP treatment were successfully identified. Based on a Gene Ontology analysis, the functions of these proteins were indicated to be closely linked with protein processing. In addition, CP treatment significantly increased the expression of calpain‑1, a calcium‑dependent intracellular cysteine protease. Furthermore, CP‑treated keratinocytes exhibited elevated interleukin (IL)‑1α and IL‑8 expression and reduced IL‑6 expression. CPs also induced the expression of proteins implicated in cell‑cell adhesion and the skin barrier. Therefore, CPs from soft‑shelled turtle may provide significant benefits for maintaining the biological environment of the skin, and may be useful as components of pharmaceuticals and medical products.

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Section: Liquid Chromatography Tandem Ms (Lc-ms/ms) Analysis For Protmentioning

confidence: 99%

Collagen peptides from soft‑shelled turtle induce calpain‑1 expression and regulate inflammatory cytokine expression in HaCaT human skin keratinocytes

et al. 2018

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“…DCs continuously monitor their environment for potential antigens and present them to T cells to induce an effector immune response or tolerance (21)(22)(23)(24). During viral infection, MoDCs change cytokine secretion levels and alter the expression of major histocompatibility complex (MHC) proteins and costimulatory molecules on the cell surface (25,26). The MHC has a critical role in the immune response against viral infections, as MHC class I (MHC-I) molecules function in antigen presentation on the cell surface for T cell recognition (27)(28)(29).…”

mentioning

confidence: 99%

Nsp1α of Porcine Reproductive and Respiratory Syndrome Virus Strain BB0907 Impairs the Function of Monocyte-Derived Dendritic Cells via the Release of Soluble CD83

Chen

Bai

Liu

et al. 2018

J Virol

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Porcine reproductive and respiratory syndrome virus (PRRSV), a virulent pathogen of swine, suppresses the innate immune response and induces persistent infection. One mechanism used by viruses to evade the immune system is to cripple the antigen-processing machinery in monocyte-derived dendritic cells (MoDCs). In this study, we show that MoDCs infected by PRRSV express lower levels of the major histocompatibility complex (MHC)-peptide complex proteins TAP1 and ERp57 and are impaired in their ability to stimulate T cell proliferation and increase their production of CD83. Neutralization of sCD83 removes the inhibitory effects of PRRSV on MoDCs. When MoDCs are incubated with exogenously added sCD83 protein, TAP1 and ERp57 expression decreases and T lymphocyte activation is impaired. PRRSV nonstructural protein 1α (Nsp1α) enhances CD83 promoter activity. Mutations in the ZF domain of Nsp1α abolish its ability to activate the CD83 promoter. We generated recombinant PRRSVs with mutations in Nsp1α and the corresponding repaired PRRSVs. Viruses with Nsp1α mutations did not decrease levels of TAP1 and ERp57, impair the ability of MoDCs to stimulate T cell proliferation, or increase levels of sCD83. We show that the ZF domain of Nsp1α stimulates the secretion of CD83, which in turn inhibits MoDC function. Our study provides new insights into the mechanisms of immune suppression by PRRSV. PRRSV has a severe impact on the swine industry throughout the world. Understanding the mechanisms by which PRRSV infection suppresses the immune system is essential for a robust and sustainable swine industry. Here, we demonstrated that PRRSV infection manipulates MoDCs by interfering with their ability to produce proteins in the MHC-peptide complex. The virus also impairs the ability of MoDCs to stimulate cell proliferation, due in large part to the enhanced release of soluble CD83 from PRRSV-infected MoDCs. The viral nonstructural protein 1 (Nsp1) is responsible for upregulating CD83 promoter activity. Amino acids in the ZF domain of Nsp1α (L5-2A, rG45A, G48A, and L61-6A) are essential for CD83 promoter activation. Viruses with mutations at these sites no longer inhibit MoDC-mediated T cell proliferation. These findings provide novel insights into the mechanism by which the adaptive immune response is suppressed during PRRSV infection.

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“…Interestingly, only CD4 + T cell modules were enriched for TNF, IL-1B, and OSM, suggesting the directed induction of pro-inflammatory T helper cells 70 . Meanwhile, monocytes and NK cells were enriched for CIITA and EBI3 (a subunit of IL-27), which regulate MHC-II and MHC-I genes, respectively 71,72 .…”

Section: Resultsmentioning

confidence: 99%

Integrated Single-Cell Analysis of Multicellular Immune Dynamics during Hyper-Acute HIV-1 Infection

Kazer

Aicher

Muema

et al. 2019

Preprint

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30Cellular immunity is critical for controlling intracellular pathogens, but the dynamics and 31 cooperativity of the evolving host response to infection are not well defined. Here, we apply single-32 cell RNA-sequencing to longitudinally profile pre-and immediately post-HIV infection peripheral 33 immune responses of multiple cell types in four untreated individuals. Onset of viremia induces a 34 strong transcriptional interferon response integrated across most cell types, with subsequent pro-35 inflammatory T cell differentiation, monocyte MHC-II upregulation, and cytolytic killing. With 36 longitudinal sampling, we nominate key intra-and extracellular drivers that induce these 37 programs, and assign their multi-cellular targets, temporal ordering, and duration in acute 38 infection. Two individuals studied developed spontaneous viral control, associated with initial 39 elevated frequencies of proliferating cytotoxic cells, inclusive of a previously unappreciated 40 proliferating natural killer (NK) cell subset. Our study presents a unified framework for 41 characterizing immune evolution during a persistent human viral infection at single-cell resolution, 42 and highlights programs that may drive response coordination and influence clinical trajectory. 43 44 54Recently, high-throughput single-cell RNA-sequencing (scRNA-Seq) has emerged as a 55 powerful tool to characterize, transcriptome-wide, complex human systems in health and disease 56 at single-cell resolution [3][4][5][6][7][8][9] . When applied to a collection of samples across a disease setting, this 57 approach provides a platform for investigating cell types, states, interactions, and drivers 58 associated with that disease; this information can be used to develop testable hypotheses on 59 therapeutic modulations that may ameliorate disease state 7,8 . Meanwhile, within an individual, 60longitudinal sampling provides an opportunity to decipher, at unprecedented resolution and 61 absent potentially confounding inter-individual variability 7 , shifts in these same variables, and to 62 3 associate observed changes with internal or external perturbations 10-12 . Such sampling of a host's 63 exposure to a pathogen could provide foundational insights into essential cellular response 64 features and their coordination, empowering the rational design of improved prophylactic 65 interventions. 66Illustratively, a better understanding of the interplay between innate and adaptive immune 67 responses at the very earliest stages of a viral infection, and its impact on long-term disease, 68 could reveal principles to accelerate prevention efforts. Human Immunodeficiency Virus (HIV) has 69 been the subject of thorough study, and thus is a well-considered model system for examining 70 host responses to a pathogen. Moreover, although the development of antiretroviral therapy 71 (ART) 13 , as well as implementation of pre-exposure prophylaxis (PrEP) 14 and combination 72 prevention efforts, has improved the lives of persons living with HIV, increased life expectancie...

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IL-27 mediates HLA class I up-regulation, which can be inhibited by the IL-6 pathway, in HLA-deficient Small Cell Lung Cancer cells

Cited by 20 publications

References 52 publications

Collagen peptides from soft‑shelled turtle induce calpain‑1 expression and regulate inflammatory cytokine expression in HaCaT human skin keratinocytes

Collagen peptides from soft‑shelled turtle induce calpain‑1 expression and regulate inflammatory cytokine expression in HaCaT human skin keratinocytes

Nsp1α of Porcine Reproductive and Respiratory Syndrome Virus Strain BB0907 Impairs the Function of Monocyte-Derived Dendritic Cells via the Release of Soluble CD83

Integrated Single-Cell Analysis of Multicellular Immune Dynamics during Hyper-Acute HIV-1 Infection

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