IRE1α activation in bone marrow-derived dendritic cells modulates innate recognition of melanoma cells and favors CD8+ T cell priming
Author
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Medel, Bernardita
Author
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Costoya, Cristobal
Author
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Fernandez, Dominique
Author
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Pereda, Cristian
Author
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Lladser, Alvaro
Author
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Sauma, Daniela
Author
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Pacheco, Rodrigo
Author
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Iwawaki, Takao
Author
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Salazar Onfray, Flavio
Author
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Osorio, Fabiola
Admission date
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2019-10-15T12:23:40Z
Available date
dc.date.available
2019-10-15T12:23:40Z
Publication date
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2019
Cita de ítem
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Frontiers in Immunology, Volumen 10, Issue JAN, 2019,
Identifier
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16643224
Identifier
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10.3389/fimmu.2018.03050
Identifier
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https://repositorio.uchile.cl/handle/2250/171591
Abstract
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The IRE1α/XBP1s signaling pathway is an arm of the unfolded protein response (UPR) that safeguards the fidelity of the cellular proteome during endoplasmic reticulum (ER) stress, and that has also emerged as a key regulator of dendritic cell (DC) homeostasis. However, in the context of DC activation, the regulation of the IRE1α/XBP1s axis is not fully understood. In this work, we report that cell lysates generated from melanoma cell lines markedly induce XBP1s and certain members of the UPR such as the chaperone BiP in bone marrow derived DCs (BMDCs). Activation of IRE1α endonuclease upon innate recognition of melanoma cell lysates was required for amplification of proinflammatory cytokine production and was necessary for efficient cross-presentation of melanoma-associated antigens without modulating the MHC-II antigen presentation machinery. Altogether, this work provides evidence indicating that ex-vivo activation of the IRE1α/XB