MFG-E8 regulates the immunogenic potential of dendritic cells primed with necrotic cell-mediated inflammatory signals.

Dendritic cells (DC) manipulate tissue homeostasis by recognizing dying cells and controlling immune functions. However, the precise mechanisms by which DC recognize different types of dying cells and devise distinct immunologic consequences remain largely obscure. Herein, we demonstrate that Milk-f...

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Autores principales:	Muhammad Baghdadi, Shigeki Chiba, Tsunaki Yamashina, Hironori Yoshiyama, Masahisa Jinushi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9a116a99191e4891bef7e7fb1c02bfff
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spelling	oai:doaj.org-article:9a116a99191e4891bef7e7fb1c02bfff2021-11-18T07:14:26ZMFG-E8 regulates the immunogenic potential of dendritic cells primed with necrotic cell-mediated inflammatory signals.1932-620310.1371/journal.pone.0039607https://doaj.org/article/9a116a99191e4891bef7e7fb1c02bfff2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22761839/?tool=EBIhttps://doaj.org/toc/1932-6203Dendritic cells (DC) manipulate tissue homeostasis by recognizing dying cells and controlling immune functions. However, the precise mechanisms by which DC recognize different types of dying cells and devise distinct immunologic consequences remain largely obscure. Herein, we demonstrate that Milk-fat globule-EGF VIII (MFG-E8) is a critical mediator controlling DC immunogenicity in inflammatory microenvironments. MFG-E8 restrains DC-mediated uptake and recognition of necrotic cells. The MFG-E8-mediated suppression of necrotic cell uptake by DC resulted in the decreased proinflammatory cytokines production and activated signal components such as STAT3 and A20, which are critical to maintain tolerogenic properties of DC. Furthermore, the DC-derived MFG-E8 negatively regulates the cross-priming and effector functions of antigen-specific T cells upon recognition of necrotic cells. MFG-E8 deficiency enhances an ability of necrotic cell-primed DC to stimulate antitumor immune responses against established tumors. Our findings define what we believe to a novel mechanism whereby MFG-E8 regulates the immunogenicity of DC by modulating the modes of recognition of dying cells. Manipulating MFG-E8 levels in DC may serve as a useful strategy for controlling inflammatory microenvironments caused by various pathological conditions including cancer and autoimmunity.Muhammad BaghdadiShigeki ChibaTsunaki YamashinaHironori YoshiyamaMasahisa JinushiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e39607 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Muhammad Baghdadi Shigeki Chiba Tsunaki Yamashina Hironori Yoshiyama Masahisa Jinushi MFG-E8 regulates the immunogenic potential of dendritic cells primed with necrotic cell-mediated inflammatory signals.
description	Dendritic cells (DC) manipulate tissue homeostasis by recognizing dying cells and controlling immune functions. However, the precise mechanisms by which DC recognize different types of dying cells and devise distinct immunologic consequences remain largely obscure. Herein, we demonstrate that Milk-fat globule-EGF VIII (MFG-E8) is a critical mediator controlling DC immunogenicity in inflammatory microenvironments. MFG-E8 restrains DC-mediated uptake and recognition of necrotic cells. The MFG-E8-mediated suppression of necrotic cell uptake by DC resulted in the decreased proinflammatory cytokines production and activated signal components such as STAT3 and A20, which are critical to maintain tolerogenic properties of DC. Furthermore, the DC-derived MFG-E8 negatively regulates the cross-priming and effector functions of antigen-specific T cells upon recognition of necrotic cells. MFG-E8 deficiency enhances an ability of necrotic cell-primed DC to stimulate antitumor immune responses against established tumors. Our findings define what we believe to a novel mechanism whereby MFG-E8 regulates the immunogenicity of DC by modulating the modes of recognition of dying cells. Manipulating MFG-E8 levels in DC may serve as a useful strategy for controlling inflammatory microenvironments caused by various pathological conditions including cancer and autoimmunity.
format	article
author	Muhammad Baghdadi Shigeki Chiba Tsunaki Yamashina Hironori Yoshiyama Masahisa Jinushi
author_facet	Muhammad Baghdadi Shigeki Chiba Tsunaki Yamashina Hironori Yoshiyama Masahisa Jinushi
author_sort	Muhammad Baghdadi
title	MFG-E8 regulates the immunogenic potential of dendritic cells primed with necrotic cell-mediated inflammatory signals.
title_short	MFG-E8 regulates the immunogenic potential of dendritic cells primed with necrotic cell-mediated inflammatory signals.
title_full	MFG-E8 regulates the immunogenic potential of dendritic cells primed with necrotic cell-mediated inflammatory signals.
title_fullStr	MFG-E8 regulates the immunogenic potential of dendritic cells primed with necrotic cell-mediated inflammatory signals.
title_full_unstemmed	MFG-E8 regulates the immunogenic potential of dendritic cells primed with necrotic cell-mediated inflammatory signals.
title_sort	mfg-e8 regulates the immunogenic potential of dendritic cells primed with necrotic cell-mediated inflammatory signals.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/9a116a99191e4891bef7e7fb1c02bfff
work_keys_str_mv	AT muhammadbaghdadi mfge8regulatestheimmunogenicpotentialofdendriticcellsprimedwithnecroticcellmediatedinflammatorysignals AT shigekichiba mfge8regulatestheimmunogenicpotentialofdendriticcellsprimedwithnecroticcellmediatedinflammatorysignals AT tsunakiyamashina mfge8regulatestheimmunogenicpotentialofdendriticcellsprimedwithnecroticcellmediatedinflammatorysignals AT hironoriyoshiyama mfge8regulatestheimmunogenicpotentialofdendriticcellsprimedwithnecroticcellmediatedinflammatorysignals AT masahisajinushi mfge8regulatestheimmunogenicpotentialofdendriticcellsprimedwithnecroticcellmediatedinflammatorysignals
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MFG-E8 regulates the immunogenic potential of dendritic cells primed with necrotic cell-mediated inflammatory signals.

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