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Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus

INTRODUCTION: Dendritic cells (DCs) are capable of inducing immunity or tolerance. Previous studies have suggested plasmacytoid DCs (pDCs) are pathogenic in systemic lupus erythematosus (SLE). However, the functional characteristics of directly isolated peripheral circulating blood pDCs in SLE have...

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Autores principales: Jin, Ou, Kavikondala, Sushma, Mok, Mo-Yin, Sun, Lingyun, Gu, Jieruo, Fu, Rong, Chan, Albert, Yeung, Joseph, Nie, Yingjie, Lau, Chak-Sing
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945027/
https://www.ncbi.nlm.nih.gov/pubmed/20618924
http://dx.doi.org/10.1186/ar3075
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author Jin, Ou
Kavikondala, Sushma
Mok, Mo-Yin
Sun, Lingyun
Gu, Jieruo
Fu, Rong
Chan, Albert
Yeung, Joseph
Nie, Yingjie
Lau, Chak-Sing
author_facet Jin, Ou
Kavikondala, Sushma
Mok, Mo-Yin
Sun, Lingyun
Gu, Jieruo
Fu, Rong
Chan, Albert
Yeung, Joseph
Nie, Yingjie
Lau, Chak-Sing
author_sort Jin, Ou
collection PubMed
description INTRODUCTION: Dendritic cells (DCs) are capable of inducing immunity or tolerance. Previous studies have suggested plasmacytoid DCs (pDCs) are pathogenic in systemic lupus erythematosus (SLE). However, the functional characteristics of directly isolated peripheral circulating blood pDCs in SLE have not been evaluated previously. METHODS: Peripheral blood pDCs from 62 healthy subjects and 58 SLE patients were treated with apoptotic cells derived from polymorphonuclear cells (PMNs). Antigen loaded or unloaded pDCs were then co-cultured with autologous or allogenous T cells. Changes in T cell proliferation, cell surface CD25 expression, intracellular Foxp3 expression and cytokine production were evaluated. pDCs that had captured apoptotic PMNs (pDCs + apoPMNs were also studied for their cytokine production (interferon (IFN)-alpha, interleukin (IL)-6, IL-10, IL-18) and toll like receptor (TLR) expression. RESULTS: Circulating pDCs from SLE patients had an increased ability to stimulate T cells when compared with control pDCs. Using allogenous T cells as responder cells, SLE pDCs induced T cell proliferation even in the absence of apoptotic PMNs. In addition, healthy pDCs + apoPMNs induced suppressive T regulatory cell features with increased Foxp3 expression in CD4 + CD25 + cells while SLE pDCs + apoPMNs did not. There were differences in the cytokine profile of pDCs that had captured apoptotic PMNs between healthy subjects and patients with SLE. Healthy pDCs + apoPMNs showed decreased production of IL-6 but no significant changes in IL-10 and IL-18. These pDCs + apoPMNs also showed increased mRNA transcription of TLR9. On the other hand, while SLE pDCs + apoPMNs also had decreased IL-6, there was decreased IL-18 mRNA expression and persistent IL-10 protein synthesis. In addition, SLE pDCs lacked TLR9 recruitment. CONCLUSIONS: We have demonstrated that peripheral circulating pDCs in patients with SLE were functionally abnormal. They lacked TLR9 expression, were less capable of inducing regulatory T cell differentiation and had persistent IL-10 mRNA expression following the capture of apoptotic PMNs. We suggest circulating pDCs may be pathogenically relevant in SLE.
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spelling pubmed-29450272010-09-25 Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus Jin, Ou Kavikondala, Sushma Mok, Mo-Yin Sun, Lingyun Gu, Jieruo Fu, Rong Chan, Albert Yeung, Joseph Nie, Yingjie Lau, Chak-Sing Arthritis Res Ther Research Article INTRODUCTION: Dendritic cells (DCs) are capable of inducing immunity or tolerance. Previous studies have suggested plasmacytoid DCs (pDCs) are pathogenic in systemic lupus erythematosus (SLE). However, the functional characteristics of directly isolated peripheral circulating blood pDCs in SLE have not been evaluated previously. METHODS: Peripheral blood pDCs from 62 healthy subjects and 58 SLE patients were treated with apoptotic cells derived from polymorphonuclear cells (PMNs). Antigen loaded or unloaded pDCs were then co-cultured with autologous or allogenous T cells. Changes in T cell proliferation, cell surface CD25 expression, intracellular Foxp3 expression and cytokine production were evaluated. pDCs that had captured apoptotic PMNs (pDCs + apoPMNs were also studied for their cytokine production (interferon (IFN)-alpha, interleukin (IL)-6, IL-10, IL-18) and toll like receptor (TLR) expression. RESULTS: Circulating pDCs from SLE patients had an increased ability to stimulate T cells when compared with control pDCs. Using allogenous T cells as responder cells, SLE pDCs induced T cell proliferation even in the absence of apoptotic PMNs. In addition, healthy pDCs + apoPMNs induced suppressive T regulatory cell features with increased Foxp3 expression in CD4 + CD25 + cells while SLE pDCs + apoPMNs did not. There were differences in the cytokine profile of pDCs that had captured apoptotic PMNs between healthy subjects and patients with SLE. Healthy pDCs + apoPMNs showed decreased production of IL-6 but no significant changes in IL-10 and IL-18. These pDCs + apoPMNs also showed increased mRNA transcription of TLR9. On the other hand, while SLE pDCs + apoPMNs also had decreased IL-6, there was decreased IL-18 mRNA expression and persistent IL-10 protein synthesis. In addition, SLE pDCs lacked TLR9 recruitment. CONCLUSIONS: We have demonstrated that peripheral circulating pDCs in patients with SLE were functionally abnormal. They lacked TLR9 expression, were less capable of inducing regulatory T cell differentiation and had persistent IL-10 mRNA expression following the capture of apoptotic PMNs. We suggest circulating pDCs may be pathogenically relevant in SLE. BioMed Central 2010 2010-07-09 /pmc/articles/PMC2945027/ /pubmed/20618924 http://dx.doi.org/10.1186/ar3075 Text en Copyright ©2010 Jin et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Jin, Ou
Kavikondala, Sushma
Mok, Mo-Yin
Sun, Lingyun
Gu, Jieruo
Fu, Rong
Chan, Albert
Yeung, Joseph
Nie, Yingjie
Lau, Chak-Sing
Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus
title Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus
title_full Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus
title_fullStr Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus
title_full_unstemmed Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus
title_short Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus
title_sort abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945027/
https://www.ncbi.nlm.nih.gov/pubmed/20618924
http://dx.doi.org/10.1186/ar3075
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