Glucocorticoids severely impair differentiation and antigen presenting function of dendritic cells despite upregulation of Toll-like receptors

Rozkova, Daniela; Horváth, Rudolf; Bartůňková, Jiřina; Špíšek, Radek

doi:10.1016/j.clim.2006.04.567

Cited by 143 publications

(110 citation statements)

References 54 publications

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“…We suggest that immature/ tolerogenic DCs (as produced by simulation by alternate CD200Rs) preferentially support development of Treg, and that TLR activation and/or cytokine administration influences DC developmental processes primarily, and Treg development (and thus immune status) secondarily. Interestingly, a recent study has suggested that immature DCs induced in the presence of chronic glucocorticoid treatment are unable to immunize, but unlike the data reported above, they are refractory to TLR stimulation (58).…”

Section: Discussioncontrasting

confidence: 49%

An Interaction between CD200 and Monoclonal Antibody Agonists to CD200R2 in Development of Dendritic Cells That Preferentially Induce Populations of CD4+CD25+ T Regulatory Cells

Gorczynski

Khatri

Lee

et al. 2008

The Journal of Immunology

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In previous studies we reported that while interaction between the relatively ubiquitously expressed molecule CD200 and one of its receptors, CD200R1, resulted in direct suppression of alloreactivity, engagement of alternate receptors led instead to altered differentiation of dendritic cells (DCs) from marrow precursors, which could in turn foster development of Foxp3+ regulatory T cells. We have explored this effect of engagement of alternate receptors by using a monoclonal agonist Ab to CD200R2 and investigating expression of TLRs on DCs induced in vivo and in vitro after CD200 stimulation in mice in which the gene encoding CD200R1 was deleted. CD200 stimulation was achieved by using either a soluble form of CD200 (CD200Fc) or overexpression of CD200 as a doxycycline-inducible transgene. Although broadly similar effects were seen, consistent with the hypothesis that triggering of CD200R2 does produce DCs with a characteristic TLR repertoire, there are subtle differences in suppression of alloreactivity achieved by CD200 delivered in these two manners, which is consistent with a complexity of CD200:CD200R engagement not previously appreciated.

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Section: Discussioncontrasting

confidence: 49%

An Interaction between CD200 and Monoclonal Antibody Agonists to CD200R2 in Development of Dendritic Cells That Preferentially Induce Populations of CD4+CD25+ T Regulatory Cells

Gorczynski

Khatri

Lee

et al. 2008

The Journal of Immunology

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“…This finding not only reflects the capacity of high-dose glucocorticoid therapy to suppress IFN, but also implies an abrogation of the antigen-presenting capacity of Siglec-1-positive resident monocytes (49,50).…”

Section: Siglec-1 As a Type 1 Interferon Surrogate Marker In Slementioning

confidence: 97%

Sialic acid–binding Ig‐like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus

Biesen¹,

Demir²,

Barkhudarova³

et al. 2008

Arthritis & Rheumatism

175

149

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Objective. Type I interferon (IFN) plays a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE) and is therefore considered a potential therapeutic target. This study was undertaken to establish a feasible biomarker for IFN effects with respect to disease activity and effectiveness of IFN-suppressive therapy in SLE patients.Methods. Transcriptomes of purified monocytes from 9 SLE patients and 7 healthy controls were analyzed by Affymetrix GeneChip technology. Levels of sialic acid-binding Ig-like lectin 1 (Siglec-1) (sialoadhesin, CD169) in inflammatory and resident monocytes were determined at the protein level in 38 healthy controls and 52 SLE patients, using multicolor flow cytometry.Results. Transcriptomes of peripheral monocytes from SLE patients revealed a dominant type I IFN signature. Siglec-1 was identified as one of the most prominent type I IFN-regulated candidate genes. At the protein level, the frequency of Siglec-1-expressing monocyte subsets was correlated with disease activity (as measured by the SLE Disease Activity Index) and was inversely correlated with levels of complement factors. Most interestingly, levels of anti-doublestranded DNA (anti-dsDNA) antibodies were highly correlated with the percentage of resident monocytes, but not inflammatory monocytes, expressing Siglec-1. High-dose glucocorticoid treatment resulted in a dramatic reduction of Siglec-1 expression in cells from patients with active SLE.Conclusion. Our findings indicate that Siglec-1 expression in resident blood monocytes is a potential biomarker for monitoring disease activity, displaying type I IFN responses, and estimating levels of antidsDNA antibodies. Moreover, our results suggest that resident and inflammatory monocytes contribute differently to the process of autoantibody formation in SLE.

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“…In vitro, purified monocytes or macrophages but not B or T cells expressed IL-10 in response to GC (Ehrchen et al, 2007;Hodge et al, 1999;Marchant et al, 1996;Mozo et al, 2004). Differentiation of dendritic cells (dc) in the presence of GC gave rise to a dc population with decreased cell surface costimulatory molecule expression and increased capacity to express IL-10 when stimulated (de Jong et al, 1999;Dong et al, 2003;Duperrier et al, 2005;Matyszak et al, 2000;Piemonti et al, 1999;Rea et al, 2000;Rozkova et al, 2006). Antigen presentation by dc in the absence of a strong costimulatory signal can drive expansion of T cells that themselves express IL-10 and have immunosuppressive "regulatory" properties (Dong et al, 2003).…”

Section: Il-10mentioning

confidence: 99%

“…GC-induced upregulation of IL-1RII has been described in a number of studies (Brown et al, 1996;Colotta et al, 1993;Ehrchen et al, 2007;Pousset et al, 2001) and may contribute to inhibition of a very specific subset of (IL-1-mediated) inflammatory responses. This decoy receptor upregulation must be seen in the context of GC-induced upregulation of several signaling receptors, such as Toll-like receptors, that can potentially transmit pro-inflammatory signals (Rozkova et al, 2006;Schleimer, 2004).…”

Section: Il-1 Receptor Type IImentioning

confidence: 99%

Anti-inflammatory functions of glucocorticoid-induced genes

Clark

2007

Molecular and Cellular Endocrinology

238

193

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Glucocorticoids severely impair differentiation and antigen presenting function of dendritic cells despite upregulation of Toll-like receptors

Cited by 143 publications

References 54 publications

An Interaction between CD200 and Monoclonal Antibody Agonists to CD200R2 in Development of Dendritic Cells That Preferentially Induce Populations of CD4+CD25+ T Regulatory Cells

An Interaction between CD200 and Monoclonal Antibody Agonists to CD200R2 in Development of Dendritic Cells That Preferentially Induce Populations of CD4+CD25+ T Regulatory Cells

Sialic acid–binding Ig‐like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus

Anti-inflammatory functions of glucocorticoid-induced genes

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