bims-unfpre 2022-03-06 papers

Issue of 2022–03–06
three papers selected by
Susan Logue, University of Manitoba

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

BMC Immunol. 2022 Mar 04. 23(1): 9

ERAP1 is a critical regulator of inflammasome-mediated proinflammatory and ER stress responses.

Maja K Blake, Patrick O'Connell, Yuliya Pepelyayeva, Sarah Godbehere, Yasser A Aldhamen, Andrea Amalfitano.

BACKGROUND: In addition to its role in antigen presentation, recent reports establish a new role for endoplasmic reticulum aminopeptidase 1 (ERAP1) in innate immunity; however, the mechanisms underlying these functions are not fully defined. We previously confirmed that loss of ERAP1 functions resulted in exaggerated innate immune responses in a murine in vivo model. Here, we investigated the role of ERAP1 in suppressing inflammasome pathways and their dependence on ER stress responses.
RESULTS: Using bone marrow-derived macrophages (BMDMs), we found that loss of ERAP1 in macrophages resulted in exaggerated production of IL-1β and IL-18 and augmented caspase-1 activity, relative to wild type macrophages. Moreover, an in vivo colitis model utilizing dextran sodium sulfate (DSS) confirmed increased levels of proinflammatory cytokines and chemokines in the colon of DSS treated ERAP1-/- mice as compared to identically stimulated WT mice. Interestingly, stimulated ERAP1-/- BMDMs and CD4+ T cells simultaneously demonstrated exaggerated ER stress, assessed by increased expression of ER stress-associated genes, a state that could be reverted to WT levels with use of the ER stress inhibitor Tauroursodeoxycholic acid (TUDCA).
CONCLUSIONS: Together, these results not only suggest that ERAP1 is important for regulating inflammasome dependent innate immune response pathways in vivo, but also propose a mechanism that underlies these changes, that may be associated with increased ER stress due to lack of normal ERAP1 functions.

Keywords: Ankylosing spondylitis; ER stress; Inflammasome; Innate immunity

DOI: https://doi.org/10.1186/s12865-022-00481-9

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