Phenotypic and functional abnormalities of bone marrow-derived dendritic cells in systemic lupus erythematosus

Nie, Ying J; Mok, Mo Yin; Chan, Godfrey Chi Fung; Chan, Albert W.; Jin, Ou; Kavikondala, S; Lie, Akw; Lau, Chak Sing

doi:10.1186/ar3018

Cited by 19 publications

(20 citation statements)

References 47 publications

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“…Activating or maturing DCs by administering agonistic anti-CD40 Abs has been shown to break tolerance (16), and the presence of CD40 on mature APCs has been noted during the initiation of T cell-dependent autoimmune responses (17,18). CD40 activation induces IL-12 production on DCs, resulting in the induction of Th1 responses (19)(20)(21).…”

Section: Ifferent Subsets Of Effector Cd4mentioning

confidence: 99%

Differential Requirements for Th1 and Th17 Responses to a Systemic Self-Antigen

Katzman

Gallo

Hoyer

et al. 2011

The Journal of Immunology

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T cell–APC interactions are essential for the initiation of effector responses against foreign and self-antigens, but the role of these interactions in generating different populations of effector T cells in vivo remains unclear. Using a model of CD4+ T cell responses to a systemic self-antigen without adjuvants or infection, we demonstrate that activation of APCs augments Th17 responses much more than Th1 responses. Recognition of systemic Ag induces tolerance in self-reactive CD4+ T cells, but induction of CD40 signaling, even under tolerogenic conditions, results in a strong, Ag-specific IL-17 response without large numbers of IFN-γ–producing cells. Transfer of the same CD4+ T cells into lymphopenic recipients expressing the self-antigen results in uncontrolled production of IL-17, IFN-γ, and systemic inflammation. If the Ag-specific T cells lack CD40L, production of IL-17 but not IFN-γ is decreased, and the survival time of recipient mice is significantly increased. In addition, transient blockade of the initial MHC class II-dependent T cell–APC interaction results in a greater reduction of IL-17 than of IFN-γ production. These data suggest that Th17 differentiation is more sensitive to T cell interactions with APCs than is the Th1 response, and interrupting this interaction, specifically the CD40 pathway, may be key to controlling Th17-mediated autoimmunity.

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Section: Ifferent Subsets Of Effector Cd4mentioning

confidence: 99%

Differential Requirements for Th1 and Th17 Responses to a Systemic Self-Antigen

Katzman

Gallo

Hoyer

et al. 2011

The Journal of Immunology

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“…Furthermore, we found that imiquimod enhanced the production of the proinflammatory cytokines IFN-γ, TNF-α, IL-6 and IL-10 in BMDCs of both MRL lpr/lpr and C57BL/6 mice. These data suggested that DCs from lupus-prone mice show a pathologic state of activation in comparison with those of age-matched control mice, which closely resembles the co-stimulatory defects and dysregulated DC activation found in humans SLE and other lupus-prone mouse models [8,9,10]. …”

Section: Discussionmentioning

confidence: 53%

“…There have been reports that abnormal phenotypes of DCs and Treg deficiencies in lupus patients and in lupus-prone mice [8,9,10]. The lupus-prone NZM2410 mice are connected to the reduction of Treg numbers.…”

Section: Introductionmentioning

confidence: 99%

Activation of Toll-like Receptor-7 Exacerbates Lupus Nephritis by Modulating Regulatory T Cells

et al. 2014

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Background: Toll-like receptor-7 (TLR7), which recognizes viral single-stranded RNA, can trigger immune complex glomerulonephritis in experimental lupus erythematosus. However, whether it modulates dendritic cells (DCs) phenotype and regulatory T cells (Treg) function is incompletely understood. Method: Splenocytes and bone marrow DCs were obtained from 5- and 20-week-old female MRL^lpr/lpr mice and C57BL/6 mice. In addition, to understand the response of Treg and DCs to TLR7 ligation in vivo, 16-week-old female MRL^lpr/lpr and C57BL/6 mice were distributed into two groups with or without intraperitoneal injections of TLR7 ligand every other day. Results: After activation with the TLR7 ligand imiquimod in vivo and vitro, DCs from imiquimod-treated MRL/lpr mice showed an altered costimulatory profile, with decreased induction of CD80, CD86, and MHCII expression, comparing to age-matched C57BL/6 control mice. There was no significant difference in the numbers of CD₄⁺CD₂₅⁺Foxp3⁺ cells after TLR7 ligation by imiquimod in MRL^lpr/lpr and control mice. Immunostaining of kidney sections of nephritic MRL/lpr mice revealed that CD11c was expressed in the infiltrated tubulointerstitial cells, and confocal microscopic analysis of renal CD11c⁺MHCII⁺, CD11c⁺CD80⁺, and CD11c⁺CD86⁺ cells showed an immature phenotype with low levels of CD80, CD86, and MHCII in imiquimod-treated MRL/lpr mice. There was no difference in the number of Foxp3 positive cells in kidneys between the imiq‑uimod and vehicle-treated groups. Conclusions: Our results suggest that activation of TLR7 exacerbated lupus nephritis by modulating the abnormally costimulatory phenotype of dendritic cells and functions of Treg in MRL/lpr mice.

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“…Decker et al reports similar results that SLE patients, in particular those in iDC stages showing, "Over-express" of CD86 [20]. Furthermore, Nie et al also reports the increased expression of CD40 and CD86 in SLE patients in iDC stages [21]. This could explain how peripheral tolerance ability of SLE patients may be impaired and lead to T cell auto-reactivity.…”

Section: Different Numbers Of Modc Idc and MDC Expressing Cd11c+/cd8mentioning

confidence: 81%

Low Level of Vitamin D Increased Dendritic Cell Maturation and Expression of Interferon-γ and Interleukin-4 in Systemic Lupus Erythematosus

Handono¹,

Daramatasia²,

Sunarti³

2012

IOSJPBS

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Vitamin D has been reported contribute to the regulation of immune responses by inhibiting DC maturation, T cell-dependent DC activation, reduce the secretion of Th1 and Th2 cytokines and induce the development of regulatory T cells. The aimed of this study to determine the association of vitamin D level with DC maturation, IFN-γ and IL-4 cytokine expression in Indonesian SLE patients.The study was conducted in fifty four active disease SLE patients (SLEDAI score>5 p = 0.433). Vitamin D (1,25(OH)2D3) serum concentration was significantly lower in Indonesian SLE patients compared with healthy controls. The low concentration was related to higher expression of CD11c+/CD86/CD40/CD83 in iDC cells and higher secretion of Th1 cytokines (IFN-γ) and Th2 cytokines (IL-4). Keywords: vitamin D, CD11c+/CD86/CD40/CD83, IFN-γ, IL-4, SLE I. BackgroundSystemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that occurs more frequently in the last decade. The etiology and pathogenesis of SLE remains unclear, however evidences suggest that deviation function of T cells, B cells, monocytes and regulatory T cells ultimately lead to systemic inflammation and tissue damages [1,2]. Although the 10-year life expectancy of SLE patients has risen significantly to 90% in developed countries, a study by Handono showed that life expectancy of SLE patients in Indonesia remains low, 70% within 5-year and 55% with in 10-year [3].A recent study concluded an association between the onset of autoimmune disease with vitamin D deficiency [4]. A high percentage of these patients have been found to live in continental/temperate climate countries [5]. Vitamin D contributes to the regulation of immune responses in several ways by inhibiting monocyte differentiation into dendritic cells (DC), inhibiting DC maturation or differentiation, and maintaining the condition of immature DC (iDC) [6]. Furthermore, it has been reported that vitamin D inhibits the activation of T cell-dependent DC [7], reduces the secretion of Th1 and Th2 cytokines and induces the development of regulatory T cells (Treg) [8].It has been known that DC maturation markers are surface molecular expression of CD11c+/CD86/CD40/CD83. Monocytes (moDC) that develope into DC are characterized by the expression of CD11c+ and lower expression of CD86/CD40/CD83 co-stimulatory molecules. However, expression of the molecules will increase in immature DC (iDC) and the highest expression occurred in mature DC (mDC).

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Phenotypic and functional abnormalities of bone marrow-derived dendritic cells in systemic lupus erythematosus

Cited by 19 publications

References 47 publications

Differential Requirements for Th1 and Th17 Responses to a Systemic Self-Antigen

Differential Requirements for Th1 and Th17 Responses to a Systemic Self-Antigen

Activation of Toll-like Receptor-7 Exacerbates Lupus Nephritis by Modulating Regulatory T Cells

Low Level of Vitamin D Increased Dendritic Cell Maturation and Expression of Interferon-γ and Interleukin-4 in Systemic Lupus Erythematosus

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