Differential Roles of Dendritic Cells in Expanding CD4 T Cells in Sepsis

Sepsis is a systemically dysregulated inflammatory syndrome, in which dendritic cells (DCs) play a critical role in coordinating aberrant immunity. The aim of this study is to shed light on the differential roles played by systemic versus mucosal DCs in regulating immune responses in sepsis. We iden...

Full description

Bibliographic Details
Main Authors: Samuel Darkwah, Nodoka Nago, Michael G. Appiah, Phyoe Kyawe Myint, Eiji Kawamoto, Motomu Shimaoka, Eun Jeong Park
Format: Article
Language:English
Published: MDPI AG 2019-07-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/7/3/52
_version_ 1819364823997087744
author Samuel Darkwah
Nodoka Nago
Michael G. Appiah
Phyoe Kyawe Myint
Eiji Kawamoto
Motomu Shimaoka
Eun Jeong Park
author_facet Samuel Darkwah
Nodoka Nago
Michael G. Appiah
Phyoe Kyawe Myint
Eiji Kawamoto
Motomu Shimaoka
Eun Jeong Park
author_sort Samuel Darkwah
collection DOAJ
description Sepsis is a systemically dysregulated inflammatory syndrome, in which dendritic cells (DCs) play a critical role in coordinating aberrant immunity. The aim of this study is to shed light on the differential roles played by systemic versus mucosal DCs in regulating immune responses in sepsis. We identified a differential impact of the systemic and mucosal DCs on proliferating allogenic CD4 T cells in a mouse model of sepsis. Despite the fact that the frequency of CD4 T cells was reduced in septic mice, septic mesenteric lymph node (MLN) DCs proved superior to septic spleen (SP) DCs in expanding allogeneic CD4 T cells. Moreover, septic MLN DCs markedly augmented the surface expression of MHC class II and CD40, as well as the messaging of interleukin-1β (IL-1β). Interestingly, IL-1β-treated CD4 T cells expanded in a dose-dependent manner, suggesting that this cytokine acts as a key mediator of MLN DCs in promoting septic inflammation. Thus, mucosal and systemic DCs were found to be functionally different in the way CD4 T cells respond during sepsis. Our study provides a molecular basis for DC activity, which can be differential in nature depending on location, whereby it induces septic inflammation or immune-paralysis.
first_indexed 2024-12-24T23:05:04Z
format Article
id doaj.art-90471cec829a48369ac9dd6818e69c75
institution Directory Open Access Journal
issn 2227-9059
language English
last_indexed 2024-12-24T23:05:04Z
publishDate 2019-07-01
publisher MDPI AG
record_format Article
series Biomedicines
spelling doaj.art-90471cec829a48369ac9dd6818e69c752022-12-21T16:35:02ZengMDPI AGBiomedicines2227-90592019-07-01735210.3390/biomedicines7030052biomedicines7030052Differential Roles of Dendritic Cells in Expanding CD4 T Cells in SepsisSamuel Darkwah0Nodoka Nago1Michael G. Appiah2Phyoe Kyawe Myint3Eiji Kawamoto4Motomu Shimaoka5Eun Jeong Park6Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, JapanDepartment of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, JapanDepartment of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, JapanDepartment of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, JapanDepartment of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, JapanDepartment of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, JapanDepartment of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, JapanSepsis is a systemically dysregulated inflammatory syndrome, in which dendritic cells (DCs) play a critical role in coordinating aberrant immunity. The aim of this study is to shed light on the differential roles played by systemic versus mucosal DCs in regulating immune responses in sepsis. We identified a differential impact of the systemic and mucosal DCs on proliferating allogenic CD4 T cells in a mouse model of sepsis. Despite the fact that the frequency of CD4 T cells was reduced in septic mice, septic mesenteric lymph node (MLN) DCs proved superior to septic spleen (SP) DCs in expanding allogeneic CD4 T cells. Moreover, septic MLN DCs markedly augmented the surface expression of MHC class II and CD40, as well as the messaging of interleukin-1β (IL-1β). Interestingly, IL-1β-treated CD4 T cells expanded in a dose-dependent manner, suggesting that this cytokine acts as a key mediator of MLN DCs in promoting septic inflammation. Thus, mucosal and systemic DCs were found to be functionally different in the way CD4 T cells respond during sepsis. Our study provides a molecular basis for DC activity, which can be differential in nature depending on location, whereby it induces septic inflammation or immune-paralysis.https://www.mdpi.com/2227-9059/7/3/52sepsisspleenmesenteric lymph nodesdendritic cellsCD4 T cellsIL-1β
spellingShingle Samuel Darkwah
Nodoka Nago
Michael G. Appiah
Phyoe Kyawe Myint
Eiji Kawamoto
Motomu Shimaoka
Eun Jeong Park
Differential Roles of Dendritic Cells in Expanding CD4 T Cells in Sepsis
Biomedicines
sepsis
spleen
mesenteric lymph nodes
dendritic cells
CD4 T cells
IL-1β
title Differential Roles of Dendritic Cells in Expanding CD4 T Cells in Sepsis
title_full Differential Roles of Dendritic Cells in Expanding CD4 T Cells in Sepsis
title_fullStr Differential Roles of Dendritic Cells in Expanding CD4 T Cells in Sepsis
title_full_unstemmed Differential Roles of Dendritic Cells in Expanding CD4 T Cells in Sepsis
title_short Differential Roles of Dendritic Cells in Expanding CD4 T Cells in Sepsis
title_sort differential roles of dendritic cells in expanding cd4 t cells in sepsis
topic sepsis
spleen
mesenteric lymph nodes
dendritic cells
CD4 T cells
IL-1β
url https://www.mdpi.com/2227-9059/7/3/52
work_keys_str_mv AT samueldarkwah differentialrolesofdendriticcellsinexpandingcd4tcellsinsepsis
AT nodokanago differentialrolesofdendriticcellsinexpandingcd4tcellsinsepsis
AT michaelgappiah differentialrolesofdendriticcellsinexpandingcd4tcellsinsepsis
AT phyoekyawemyint differentialrolesofdendriticcellsinexpandingcd4tcellsinsepsis
AT eijikawamoto differentialrolesofdendriticcellsinexpandingcd4tcellsinsepsis
AT motomushimaoka differentialrolesofdendriticcellsinexpandingcd4tcellsinsepsis
AT eunjeongpark differentialrolesofdendriticcellsinexpandingcd4tcellsinsepsis