IRE1α Activation in Bone Marrow-Derived Dendritic Cells Modulates Innate Recognition of Melanoma Cells and Favors CD8 + T Cell Priming

Bernardita Medel, Cristobal Costoya, Dominique Fernandez, Cristian Pereda, Alvaro Lladser, Daniela Sauma, Rodrigo Pacheco, Takao Iwawaki, Flavio Salazar-Onfray, Fabiola Osorio

Resultado de la investigación: Article

3 Citas (Scopus)

Resumen

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/XBP1 pathway in BMDCs enhances CD8+ T cell specific responses against tumor antigens.

Idioma originalEnglish
Número de páginas1
PublicaciónFrontiers in Immunology
Volumen9
DOI
EstadoPublished - 4 ene 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Citar esto

Medel, Bernardita ; Costoya, Cristobal ; Fernandez, Dominique ; Pereda, Cristian ; Lladser, Alvaro ; Sauma, Daniela ; Pacheco, Rodrigo ; Iwawaki, Takao ; Salazar-Onfray, Flavio ; Osorio, Fabiola. / IRE1α Activation in Bone Marrow-Derived Dendritic Cells Modulates Innate Recognition of Melanoma Cells and Favors CD8 + T Cell Priming. En: Frontiers in Immunology. 2019 ; Vol. 9.
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title = "IRE1α Activation in Bone Marrow-Derived Dendritic Cells Modulates Innate Recognition of Melanoma Cells and Favors CD8 + T Cell Priming",
abstract = "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/XBP1 pathway in BMDCs enhances CD8+ T cell specific responses against tumor antigens.",
keywords = "IRE1α, UPR, XBP1s, cross-presentation, dendritic cell, melanoma",
author = "Bernardita Medel and Cristobal Costoya and Dominique Fernandez and Cristian Pereda and Alvaro Lladser and Daniela Sauma and Rodrigo Pacheco and Takao Iwawaki and Flavio Salazar-Onfray and Fabiola Osorio",
year = "2019",
month = "1",
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doi = "10.3389/fimmu.2018.03050",
language = "English",
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Medel, B, Costoya, C, Fernandez, D, Pereda, C, Lladser, A, Sauma, D, Pacheco, R, Iwawaki, T, Salazar-Onfray, F & Osorio, F 2019, 'IRE1α Activation in Bone Marrow-Derived Dendritic Cells Modulates Innate Recognition of Melanoma Cells and Favors CD8 + T Cell Priming', Frontiers in Immunology, vol. 9. https://doi.org/10.3389/fimmu.2018.03050

IRE1α Activation in Bone Marrow-Derived Dendritic Cells Modulates Innate Recognition of Melanoma Cells and Favors CD8 + T Cell Priming. / Medel, Bernardita; Costoya, Cristobal; Fernandez, Dominique; Pereda, Cristian; Lladser, Alvaro; Sauma, Daniela; Pacheco, Rodrigo; Iwawaki, Takao; Salazar-Onfray, Flavio; Osorio, Fabiola.

En: Frontiers in Immunology, Vol. 9, 04.01.2019.

Resultado de la investigación: Article

TY - JOUR

T1 - IRE1α Activation in Bone Marrow-Derived Dendritic Cells Modulates Innate Recognition of Melanoma Cells and Favors CD8 + T Cell Priming

AU - Medel, Bernardita

AU - Costoya, Cristobal

AU - Fernandez, Dominique

AU - Pereda, Cristian

AU - Lladser, Alvaro

AU - Sauma, Daniela

AU - Pacheco, Rodrigo

AU - Iwawaki, Takao

AU - Salazar-Onfray, Flavio

AU - Osorio, Fabiola

PY - 2019/1/4

Y1 - 2019/1/4

N2 - 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/XBP1 pathway in BMDCs enhances CD8+ T cell specific responses against tumor antigens.

AB - 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/XBP1 pathway in BMDCs enhances CD8+ T cell specific responses against tumor antigens.

KW - IRE1α

KW - UPR

KW - XBP1s

KW - cross-presentation

KW - dendritic cell

KW - melanoma

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U2 - 10.3389/fimmu.2018.03050

DO - 10.3389/fimmu.2018.03050

M3 - Article

VL - 9

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

ER -