Maturation-dependent expression of C1q binding proteins on the cell surface of human monocyte-derived dendritic cells

Végh, Zsuzsa; Goyarts, E.; Rozengarten, Kimberly; Mazumder, Amitabha; Ghebrehiwet, Berhane

doi:10.1016/s1567-5769(02)00211-4

Cited by 38 publications

(18 citation statements)

References 35 publications

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“…Recently, the presence of CRT on the surface of monocyte-derived DC was reported (23). Immature DC selectively express higher levels of surface CRT than mature ones while the total level of CRT protein and RNA remain the same (23), which agrees with our observation that DC matured by certain approaches have a slight lower binding to NY-ESO-1. Immature DC surface CRT is also a critical component of the early phagosome that is fused with ER-derived membranes soon after phagocytosis (14,24).…”

Section: Discussionsupporting

confidence: 88%

“…Third, the CRT/CD91 complex on macrophages is responsible for inflammation in response to lung collectins complexed with necrotic bodies (22). Recently, the presence of CRT on the surface of monocyte-derived DC was reported (23). Immature DC selectively express higher levels of surface CRT than mature ones while the total level of CRT protein and RNA remain the same (23), which agrees with our observation that DC matured by certain approaches have a slight lower binding to NY-ESO-1.…”

Section: Discussionmentioning

confidence: 99%

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Dendritic Cell Surface Calreticulin Is a Receptor for NY-ESO-1: Direct Interactions between Tumor-Associated Antigen and the Innate Immune System

Zeng

Aldridge²,

Tian³

et al. 2006

The Journal of Immunology

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How the immune system recognizes endogenously arising tumors and elicits adaptive immune responses against nonmutated tumor-associated Ags is poorly understood. In search of intrinsic factors contributing to the immunogenicity of the tumor-associated Ag NY-ESO-1, we found that the NY-ESO-1 protein binds to the surface of immature dendritic cells (DC), macrophages, and monocytes, but not to that of B cells or T cells. Using immunoprecipitation coupled with tandem mass spectrometry, we isolated DC surface calreticulin as the receptor for NY-ESO-1. Calreticulin Abs blocked NY-ESO-1 binding on immature DC and its cross-presentation to CD8+ T cells in vitro. Calreticulin/NY-ESO-1 interactions provide a direct link between NY-ESO-1, the innate immune system, and, potentially, the adaptive immune response against NY-ESO-1.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Dendritic Cell Surface Calreticulin Is a Receptor for NY-ESO-1: Direct Interactions between Tumor-Associated Antigen and the Innate Immune System

Zeng

Aldridge²,

Tian³

et al. 2006

The Journal of Immunology

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“…The described activity of C1q on DC might be mediated by specific interactions with C1q receptors present on monocytes and DC [33,41,42]. C1q can bind to monocytes as well as immature DC, while a reduced binding occurs on activated DC [42].…”

Section: Discussionmentioning

confidence: 99%

Immune modulation of human dendritic cells by complement

et al. 2007

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Deficiency in complement proteins such as C1q is associated with the development of systemic lupus erythematosus (SLE). Here, we show that the differentiation of dendritic cells (DC) in the presence of C1q (C1qDC) gives rise to CD1a + /DC-SIGN + cells with high phagocytic capacity and low expression of CD80, CD83 and CD86. Further, when C1qDC were exposed to LPS, a significant reduction in the production of IL-6, TNF-a and IL-10 occurred with a limited up-regulation of CD80, CD83 and CD86. In addition, C1qDC were less responsive to activation by CD40L in terms of IL-12p70 secretion and CD86 expression. C1qDC showed an impaired ability to stimulate alloreactive T cells, with a reduced production of IFN-c. In conclusion, we have shown that C1q is a potent modulator of DC, resulting in cells characterized by an impaired capacity of cytokine production and an impaired up-regulation of costimulatory molecules, leading to a limited T cell response. Therefore, we hypothesize that, next to a pivotal role in the safe clearance of apoptotic cells, C1q regulates the threshold of DC activation and thereby prevents hyperactivation of the overall immune response.

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“…Dendritic cells (DCs) are professional APCs that specialize in antigen capture and T-cell priming. DCs express a large repertoire of complement receptors on their surface 3 and are the source of many complement components. The first component of the classical complement pathway, C1q, is primarily produced by DCs and macrophages, whereas most other complement factors originate in the liver.…”

Section: Introductionmentioning

confidence: 99%

C1q enhances IFN-γ production by antigen-specific T cells via the CD40 costimulatory pathway on dendritic cells

Baruah¹,

Dumitriu²,

Malik³

et al. 2009

Blood

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Dendritic cells (DCs) are known to produce C1q, the initiator of the classical complement pathway. We demonstrate that murine DCs deficient in C1q (C1qa Ϫ/Ϫ ) are poorer than wild-type (WT) DCs at eliciting the proliferation and Th1 differentiation of antigenspecific T cells. These defects result from decreased production of IL-12p70 by C1qa Ϫ/Ϫ DCs and impaired expression of costimulatory molecules CD80 and CD86 in response to CD40 ligation. The defective production of IL-12p70 and the reduced expression of CD80 and CD86 by C1qa Ϫ/Ϫ DCs were specifically mediated via CD40 ligation, as normal levels of IL-12p70 and CD80/86 were observed after ligation of Tolllike receptors (TLRs) on C1qa Ϫ/Ϫ DCs. CD40 ligation on C1qa Ϫ/Ϫ DCs, but not TLR ligation, results in decreased phosphorylation of p38 and ERK1/2 kinases. A strong colocalization of CD40 and C1q was observed by confocal microscopy upon CD40 ligation (but not TLR ligation) on DCs. Furthermore, human DCs from 2 C1q-deficient patients were found to have impaired IL-12p70 production in response to CD40L stimulation. Our novel data suggest that C1q augments the production of IL-12p70 by mouse and human DCs after CD40 triggering and plays important roles in sustaining the maturation of DCs and guiding the activation of T cells.

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Maturation-dependent expression of C1q binding proteins on the cell surface of human monocyte-derived dendritic cells

Cited by 38 publications

References 35 publications

Dendritic Cell Surface Calreticulin Is a Receptor for NY-ESO-1: Direct Interactions between Tumor-Associated Antigen and the Innate Immune System

Dendritic Cell Surface Calreticulin Is a Receptor for NY-ESO-1: Direct Interactions between Tumor-Associated Antigen and the Innate Immune System

Immune modulation of human dendritic cells by complement

C1q enhances IFN-γ production by antigen-specific T cells via the CD40 costimulatory pathway on dendritic cells

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