bims-ershed 2022-03-06 papers

Front Immunol. 2022 ;13 823157

The Unfolded Protein Response at the Tumor-Immune Interface.

Maurizio Zanetti, Su Xian, Magalie Dosset, Hannah Carter.

The tumor-immune interface has surged to primary relevance in an effort to understand the hurdles facing immune surveillance and cancer immunotherapy. Reports over the past decades have indicated a role for the unfolded protein response (UPR) in modulating not only tumor cell fitness and drug resistance, but also local immunity, with emphasis on the phenotype and altered function of immune cells such as myeloid cells and T cells. Emerging evidence also suggests that aneuploidy correlates with local immune dysregulation. Recently, we reported that the UPR serves as a link between aneuploidy and immune cell dysregulation in a cell nonautonomous way. These new findings add considerable complexity to the organization of the tumor microenvironment (TME) and the origin of its altered function. In this review, we summarize these data and also discuss the role of aneuploidy as a negative regulator of local immunity.

Keywords: T cells; aneuploidy; myeloid cells; transcellular stress; unfolded protein response (UPR)

DOI: https://doi.org/10.3389/fimmu.2022.823157

iScience. 2022 Mar 18. 25(3): 103877

A plant receptor domain with functional analogies to animal malectin disables ER stress responses upon infection.

Laïla Giordano, Valérie Allasia, Alexandra Cremades, Sophie Hok, Franck Panabières, Béatrice Bailly-Maître, Harald Keller.

Malectins from the oligosaccharyltransferase (OST) complex in the endoplasmic reticulum (ER) of animal cells are involved in ER quality control and contribute to the Unfolded Protein Response (UPR). Malectins are not found in plant cells, but malectin-like domains (MLDs) are constituents of many membrane-bound receptors. In Arabidopsis thaliana, the MLD-containing receptor IOS1 promotes successful infection by filamentous plant pathogens. We show that the MLD of its exodomain retains IOS1 in the ER of plant cells and attenuates the infection-induced UPR. Expression of the MLD in the ios1-1 knockout background is sufficient to complement infection-related phenotypes of the mutant, such as increased UPR and reduced disease susceptibility. IOS1 interacts with the ER membrane-associated ribophorin HAP6 from the OST complex, and hap6 mutants show decreased pathogen-responsive UPR and increased disease susceptibility. Altogether, this study revealed a previously uncharacterized role of a plant receptor domain in the regulation of ER stress during infection.

Keywords: Molecular biology; Plant biology; Plant pathology

DOI: https://doi.org/10.1016/j.isci.2022.103877

DNA Repair (Amst). 2022 Apr;pii: S1568-7864(22)00030-1. [Epub ahead of print]112 103301

Histone variants: The unsung guardians of the genome.

Ernest O N Phillips, Akash Gunjan.

Histones H2A, H2B, H3, H4 and H1 are highly conserved, positively charged proteins which form a disc-shaped protein core around which genomic DNA is wrapped to form a nucleosome. Immediately following DNA synthesis, replication-dependent canonical histones help package the DNA into nucleosomes to form compact chromatin fibers that can fit within the confines of the cell nucleus. Histone variants, which vary from the canonical histones in their primary amino acid sequence and expression patterns, replace their canonical counterparts throughout the cell cycle in important biological processes such as transcription, replication, DNA repair and heterochromatin formation. DNA damage is a continual threat to genomic stability and cell survival. Unrepaired DNA lesions are either lethal or can promote mutations if the damaged cells escape programmed cell death due to apoptosis. In order to repair DNA damage, cells use multiple DNA repair pathways, all of which require the recruitment of a multiple DNA damage signaling and repair factors. In order for these repair factors to be recruited efficiently and function properly at sites of DNA damage, the local chromatin environment surrounding the DNA lesion is often altered. Cells are able to regulate chromatin structure in the vicinity of DNA lesions through the addition of posttranslational modifications on histones and DNA, as well as through histone variant incorporation or removal. Recruitment or removal of histone variants at sites of DNA damage can alter the local chromatin structure by destabilizing it and making it more accessible to repair factors. Alternatively, some histone variants and their modifications may also provide specific binding sites for the recruitment of various DNA repair factors, thereby influencing repair pathway choice or repair efficiency, or both. This review seeks to provide an overview of our current understanding of the roles played by histone variants in DNA repair, especially in mammalian cells.

Keywords: Cancer; Chromatin; DNA damage; DNA repair; Genome stability; Histone variant

DOI: https://doi.org/10.1016/j.dnarep.2022.103301

J Agric Food Chem. 2022 Mar 01.

Preventive Effect of Apple Polyphenol Extract on High-Fat Diet-Induced Hepatic Steatosis in Mice through Alleviating Endoplasmic Reticulum Stress.

Bei Yan, Lei Chen, Yanhui Wang, Jiacheng Zhang, Hui Zhao, Qinglian Hua, Shengjie Pei, Zihang Yue, Hui Liang, Huaqi Zhang.

In this work, the protective effect of apple polyphenol extract (APE) on hepatic steatosis was investigated. Thirty-two C57BL/6J mice were assigned randomly to control group, hepatic steatosis group, lovastatin group, and APE group. After 8 weeks of intervention, APE supplementation markedly decreased the body weight gain, liver weight, liver index, epididymal adipose weight, epididymal adipose index, serum, and hepatic lipid levels. Hematoxylin and eosin staining revealed that APE supplementation alleviated histopathological changes of hepatic steatosis. Western blot revealed that APE downregulated the protein levels of GRP78, IRE1α, p-IRE1α, XBP1, PERK, p-PERK, p-eIF2α, ATF6, PPAR-γ, SREBP-1c, FAS, and ACC1. In conclusion, this study found that APE inhibited IRE1α-XBP1, PERK-eIF2α, and ATF6 signaling pathways to alleviate endoplasmic reticulum stress, thereby improving HFD-induced hepatic steatosis.

Keywords: apple polyphenol; endoplasmic reticulum stress; hepatic steatosis

DOI: https://doi.org/10.1021/acs.jafc.1c07733

South Med J. 2022 Mar;115(3): 227-231

Neurocognitive Rehabilitation in COVID-19 Patients: A Clinical Review.

Ryan Mathern, Pooja Senthil, Nguyen Vu, Thanigaiarsu Thiyagarajan.

Abstract: COVID-19 has affected many people all around the world for more than two years now have suffered many long-term consequences which is commonly referred to as long-haulers. Despite multiorgan complaints in long haulers, symptoms related to cognitive functions commonly referred as brain fog are seen in the high risk covid patients with age more than 50, women more than men, obesity, asthma and those who experienced more than five symptoms during the first week of covid illness. Long term isolation has certainly contributed to high level of anxiety and stress calling for an empathetic response to this group of covid patients as there is no specific test to detect long haulers and no specific cognitive rehabilitation techniques available as of today.

DOI: https://doi.org/10.14423/SMJ.0000000000001371