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Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus.
Arthritis Res Ther. 2010; 12(4):R137.AR

Abstract

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.

Authors+Show Affiliations

Department of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. jinouwishugood@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20618924

Citation

Jin, Ou, et al. "Abnormalities in Circulating Plasmacytoid Dendritic Cells in Patients With Systemic Lupus Erythematosus." Arthritis Research & Therapy, vol. 12, no. 4, 2010, pp. R137.
Jin O, Kavikondala S, Mok MY, et al. Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus. Arthritis Res Ther. 2010;12(4):R137.
Jin, O., Kavikondala, S., Mok, M. Y., Sun, L., Gu, J., Fu, R., Chan, A., Yeung, J., Nie, Y., & Lau, C. S. (2010). Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus. Arthritis Research & Therapy, 12(4), R137. https://doi.org/10.1186/ar3075
Jin O, et al. Abnormalities in Circulating Plasmacytoid Dendritic Cells in Patients With Systemic Lupus Erythematosus. Arthritis Res Ther. 2010;12(4):R137. PubMed PMID: 20618924.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus. AU - Jin,Ou, AU - Kavikondala,Sushma, AU - Mok,Mo-Yin, AU - Sun,Lingyun, AU - Gu,Jieruo, AU - Fu,Rong, AU - Chan,Albert, AU - Yeung,Joseph, AU - Nie,Yingjie, AU - Lau,Chak-Sing, Y1 - 2010/07/09/ PY - 2009/10/13/received PY - 2010/05/12/revised PY - 2010/07/09/accepted PY - 2010/7/13/entrez PY - 2010/7/14/pubmed PY - 2011/1/20/medline SP - R137 EP - R137 JF - Arthritis research & therapy JO - Arthritis Res. Ther. VL - 12 IS - 4 N2 - 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. SN - 1478-6362 UR - https://www.unboundmedicine.com/medline/citation/20618924/Abnormalities_in_circulating_plasmacytoid_dendritic_cells_in_patients_with_systemic_lupus_erythematosus_ L2 - https://arthritis-research.biomedcentral.com/articles/10.1186/ar3075 DB - PRIME DP - Unbound Medicine ER -