Endoplasmic Reticulum Quality Control in Immune Cells

Jiang, Yalan; Tao, Zehua; Chen, Hua; Sheng, Xia

doi:10.3389/fcell.2021.740653

Cited by 18 publications

(19 citation statements)

References 147 publications

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“…OSR scores were highest in epithelial, myeloid, pericytes and fibroblasts (Figure 2E; Supplementary Figure 1A), while the hypoxia stress response was highest in endothelial cells in breast, pancreas, and prostate tumors, and was among the highest in the endothelial cells of ovarian tumors (Figure 2F; Supplementary Figure 1B). HSR scores were divergent in their distribution across cell types in the different tumors (Figure 2G; Supplementary Figure 1C), and B cells expressed high UPR scores in all tumors, potentially due to the protein folding stress associated with the requirement to translate and sustain a high level of antibodies (Jiang et al , 2021) (Figure 2H; Supplementary Figure 1D). T, B, and myeloid cells expressed high DNA damage response scores in all tumors (Figure 2I; Supplementary Figure 1E).…”

Section: Resultsmentioning

confidence: 99%

Mapping the tumor stress network reveals dynamic shifts in the stromal oxidative stress response

Lior,

Barki,

Iacobuzio-Donahue

et al. 2023

Preprint

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The tumor microenvironment (TME) is a challenging environment where cells must cope with stressful conditions such as fluctuating pH levels, hypoxia, and free radicals. In response, stress pathways are activated, which can both promote and inhibit tumorigenesis. In this study, we set out to characterize the stress response landscape across four carcinomas: breast, pancreas, ovary, and prostate tumors, focusing on five pathways: Heat shock response, oxidative stress response, unfolded protein response, hypoxia stress response, and DNA damage response. Using a combination of experimental and computational methods, we create an atlas of the stress response landscape across various types of carcinomas. We find that stress responses are heterogeneously activated in the TME, and highly activated near cancer cells. Focusing on the non-immune stroma we find, across tumor types, that NRF2 and the oxidative stress response are distinctly activated in immune-regulatory cancer-associated fibroblasts and in a unique subset of cancer associated pericytes. Our study thus provides an interactome of stress responses in cancer, offering new ways to intersect survival pathways within the tumor, and advance cancer therapy.

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Section: Resultsmentioning

confidence: 99%

Mapping the tumor stress network reveals dynamic shifts in the stromal oxidative stress response

Lior,

Barki,

Iacobuzio-Donahue

et al. 2023

Preprint

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“…A group of TFs with high activity were also revealed in cluster T9, including AP-1, NF-κB, CREM, BHLHE40, STAT3, and stress-response sensors HIF1α, ATF4, and DDIT3. BHLHE40 is a stress-responsive TF that promotes inflammatory Th1 cell differentiation while CREM is a cAMP-dependent TF that promotes oxidative phosphorylation, STAT3 expression, and IL-17 expression ( 50 – 52 ). These transcriptome features indicate that the cells in cluster T9 undergo high level of endoplasmic reticulum (ER) stress that may lead to dysregulated effector T-cell survival and/or differentiation ( 53 – 55 ).…”

Section: Resultsmentioning

confidence: 99%

Landscape of Peripheral Blood Mononuclear Cells and Soluble Factors in Severe COVID-19 Patients With Pulmonary Fibrosis Development

et al. 2022

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Resulting from severe inflammation and cell destruction, COVID-19 patients could develop pulmonary fibrosis (PF), which remains in the convalescent stage. Nevertheless, how immune response participates in the pathogenesis of PF progression is not well defined. To investigate that question, 12 patients with severe COVID-19 were included in the study. Peripheral mononuclear cell (PBMC) samples were collected shortly after their admission and proceeded for single-cell RNA sequencing (scRNA-seq). After 14 days of discharge, the patients were revisited for chest CT scan. PF index (FI) was computed by AI-assisted CT images. Patients were categorized into FIhi and FIlo based on median of FI. By scRNA-seq analysis, our data demonstrated that frequency of CD4+ activated T cells and Treg cells were approximately 3-fold higher in FIhi patients compared with FIlo ones (p < 0.034 for all). By dissecting the differentially expressed genes, we found an overall downregulation of IFN-responsive genes (STAT1, IRF7, ISG15, ISG20, IFIs, and IFITMs) and S100s alarmins (S100A8, S100A9, S100A12, etc.) in all T-cell clusters, and cytotoxicity-related genes (GZMB, PRF1, and GNLY) in CTLs and γδ T cells in the FIhi cohort, compared with FIlo subjects. The GSEA analysis illustrated decreased expression of genes enriched in IFN signaling, innate immune response, adaptive immune response in T cells, NK cells, and monocytes in FIhi patients compared with FIlo ones. In conclusion, these data indicated that the attenuated IFN-responsive genes and their related signaling pathways could be critical for PF progression in COVID-19 patients.

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“…Myeloid progenitor cells MP and lymphoid progenitor cells LP are multipotent stem cells that can give rise to a variety of immune cell types. The ERQC system has been shown in the literature to be critical for immune cell maturation and function [ 180 ].…”

Section: Stress In Endoplasmic Reticulum a Major Driver Of Mdsc Influ...mentioning

confidence: 99%

Myeloid-Derived Suppressor Cells in Cancer and COVID-19 as Associated with Oxidative Stress

et al. 2023

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Myeloid-derived suppressor cells MDSCs are a heterogeneous population of cells that expand beyond their physiological regulation during pathologies such as cancer, inflammation, bacterial, and viral infections. Their key feature is their remarkable ability to suppress T cell and natural killer NK cell responses. Certain risk factors for severe COVID-19 disease, such as obesity and diabetes, are associated with oxidative stress. The resulting inflammation and oxidative stress can negatively impact the host. Similarly, cancer cells exhibit a sustained increase in intrinsic ROS generation that maintains the oncogenic phenotype and drives tumor progression. By disrupting endoplasmic reticulum calcium channels, intracellular ROS accumulation can disrupt protein folding and ultimately lead to proteostasis failure. In cancer and COVID-19, MDSCs consist of the same two subtypes (PMN-MSDC and M-MDSC). While the main role of polymorphonuclear MDSCs is to dampen the response of T cells and NK killer cells, they also produce reactive oxygen species ROS and reactive nitrogen species RNS. We here review the origin of MDSCs, their expansion mechanisms, and their suppressive functions in the context of cancer and COVID-19 associated with the presence of superoxide anion •O2− and reactive oxygen species ROS.

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Endoplasmic Reticulum Quality Control in Immune Cells

Cited by 18 publications

References 147 publications

Mapping the tumor stress network reveals dynamic shifts in the stromal oxidative stress response

Mapping the tumor stress network reveals dynamic shifts in the stromal oxidative stress response

Landscape of Peripheral Blood Mononuclear Cells and Soluble Factors in Severe COVID-19 Patients With Pulmonary Fibrosis Development

Myeloid-Derived Suppressor Cells in Cancer and COVID-19 as Associated with Oxidative Stress

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