Article: Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus
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- Publisher Website: 10.1186/ar3075
- Scopus: eid_2-s2.0-77954339436
- PMID: 20618924
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| Title | Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Jin, O1 2 Kavikondala, S1 Mok, MY1 Sun, L3 Gu, J2 Fu, R1 Chan, A1 Yeung, J1 Nie, Y1 Lau, CS1 | ||||||
| Issue Date | 2010 | ||||||
| Publisher | BioMed Central Ltd. The Journal's web site is located at http://arthritis-research.com/ | ||||||
| Citation | Arthritis Research And Therapy, 2010, v. 12 n. 4 [How to Cite?] DOI: http://dx.doi.org/10.1186/ar3075 | ||||||
| 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. © 2010 Jin et al.; licensee BioMed Central Ltd. | ||||||
| ISSN | 1478-6354 2011 Impact Factor: 4.445 2011 SCImago Journal Rankings: 0.482 | ||||||
| DOI | http://dx.doi.org/10.1186/ar3075 | ||||||
| ISI Accession Number ID | WOS:000283841500011
Funding Information: This study was funded by the University Grants Council research grant and The Government of Hong Kong SAR. We thank Miss Ivy Law for her help in drawing blood and Dr. Li-wei Lu and Mr. Otis Ko for their technological suggestions. We thank Miss Helen Law, Dr. Yu-lung Lau and Dr. Eddie Ip for their kind help in the initial stage of setting up the experiments. Thanks are also due to Miss Jessie Wong for her secretarial help and all the subjects who took part in the experiments. | ||||||
| PubMed Central ID | PMC2945027 | ||||||
| References | References in Scopus |
| dc.contributor.author | Jin, O | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Kavikondala, S | ||||||
| dc.contributor.author | Mok, MY | ||||||
| dc.contributor.author | Sun, L | ||||||
| dc.contributor.author | Gu, J | ||||||
| dc.contributor.author | Fu, R | ||||||
| dc.contributor.author | Chan, A | ||||||
| dc.contributor.author | Yeung, J | ||||||
| dc.contributor.author | Nie, Y | ||||||
| dc.contributor.author | Lau, CS | ||||||
| dc.date.accessioned | 2010-10-31T11:05:41Z | ||||||
| dc.date.available | 2010-10-31T11:05:41Z | ||||||
| dc.date.issued | 2010 | ||||||
| dc.description.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. © 2010 Jin et al.; licensee BioMed Central Ltd. | ||||||
| dc.description.nature | published_or_final_version | ||||||
| dc.identifier.citation | Arthritis Research And Therapy, 2010, v. 12 n. 4 [How to Cite?] DOI: http://dx.doi.org/10.1186/ar3075 | ||||||
| dc.identifier.citeulike | 7470065 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1186/ar3075 | ||||||
| dc.identifier.hkuros | 195373 | ||||||
| dc.identifier.hkuros | 174742 | ||||||
| dc.identifier.isi | WOS:000283841500011
Funding Information: This study was funded by the University Grants Council research grant and The Government of Hong Kong SAR. We thank Miss Ivy Law for her help in drawing blood and Dr. Li-wei Lu and Mr. Otis Ko for their technological suggestions. We thank Miss Helen Law, Dr. Yu-lung Lau and Dr. Eddie Ip for their kind help in the initial stage of setting up the experiments. Thanks are also due to Miss Jessie Wong for her secretarial help and all the subjects who took part in the experiments. | ||||||
| dc.identifier.issn | 1478-6354 2011 Impact Factor: 4.445 2011 SCImago Journal Rankings: 0.482 | ||||||
| dc.identifier.issue | 4 | ||||||
| dc.identifier.openurl | | ||||||
| dc.identifier.pmcid | PMC2945027 | ||||||
| dc.identifier.pmid | 20618924 | ||||||
| dc.identifier.scopus | eid_2-s2.0-77954339436 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/124996 | ||||||
| dc.identifier.volume | 12 | ||||||
| dc.language | eng | ||||||
| dc.publisher | BioMed Central Ltd. The Journal's web site is located at http://arthritis-research.com/ | ||||||
| dc.publisher.place | United Kingdom | ||||||
| dc.relation.ispartof | Arthritis Research and Therapy | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | Creative Commons: Attribution 3.0 Hong Kong License | ||||||
| dc.rights | Arthritis Research & Therapy. Copyright © BioMed Central Ltd. | ||||||
| dc.subject.mesh | Adult | ||||||
| dc.subject.mesh | Avian Proteins - metabolism | ||||||
| dc.subject.mesh | Cell Division - immunology | ||||||
| dc.subject.mesh | Dendritic Cells - immunology - metabolism - pathology | ||||||
| dc.subject.mesh | Lupus Erythematosus, Systemic - immunology - pathology | ||||||
| dc.title | Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- Third Affiliated Hospital of Sun Yat-Sen Uviversity
- The Affiliated DrumTower Hospital of Nanjing University Medical School