IRE1α activation in bone marrow-derived dendritic cells modulates innate recognition of melanoma cells and favors CD8+ T cell priming

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Miniatura
Fecha
2019-01
Profesor/a Guía
Facultad/escuela
Idioma
en
Título de la revista
ISSN de la revista
Título del volumen
Editor
Frontiers Media S.A.
Nombre de Curso
Licencia CC
Atribución 4.0 Internacional (CC BY 4.0)
Licencia CC
https://creativecommons.org/licenses/by/4.0/deed.es
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. © 2007 - 2019 Frontiers Media S.A. All Rights Reserved.
Notas
Indexación: Scopus
Palabras clave
Cross-presentation, Dendritic cell, IRE1α, Melanoma, UPR, XBP1s
Citación
Frontiers in Immunology Volume 10, Issue JAN2019 Article number 3050
DOI
10.3389/fimmu.2018.03050
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