Dendritic Cell Development and Survival Require Distinct NF-κB Subunits

Ouaaz, F; Arron, Joseph R.; Zheng, Ye; Choi, Yongwon; Beg, Amer A.

doi:10.1016/s1074-7613(02)00272-8

Cited by 357 publications

(331 citation statements)

References 51 publications

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“…In addition, B-cells derived from nfkb1 -/-, rela -/-tnfr1 -/-or crel -/-mice exhibited proliferation defects in vitro (Alcamo et al, 2002;Kontgen et al, 1995;Sha et al, 1995). Similar studies have also established an important role for canonical NF-κB dimers in thymocyte maturation (Boothby et al, 1997), T-cell proliferation, survival and in vivo function (Zheng et al, 2003), and in dendritic cell development (Ouaaz et al, 2002). In sum, these genetic analyses have established a role for the canonical NF-κB pathway in innate and adaptive immune compartments, in both cell activation and development.…”

Section: Mouse Genetics Indicate Diverse Canonical Nf-κb Functions Inmentioning

confidence: 75%

Crosstalk via the NF-κB signaling system

Basak¹,

Hoffmann²

2008

Cytokine & Growth Factor Reviews

153

117

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The NF-κB family of transcription factors consists of fifteen possible dimers whose activity is controlled by a family of inhibitor proteins, known as IκBs. A variety of cellular stimuli, many of them transduced by members of the TNFR superfamily, induce degradation of IκBs to activate an overlapping subset of NF-κB dimers. However, generation and stimulus-responsive activation of NF-κB dimers are intimately linked via various cross-regulatory mechanisms that allow crosstalk between different signaling pathways through the NF-κB signaling system. In this review, we summarize these mechanisms and discuss physiological and pathological consequences of crosstalk between apparently distinct inflammatory and developmental signals. We argue that a systems approach will be valuable for understanding questions of specificity and emergent properties of highly networked cellular signaling systems.

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Section: Mouse Genetics Indicate Diverse Canonical Nf-κb Functions Inmentioning

confidence: 75%

Crosstalk via the NF-κB signaling system

Basak¹,

Hoffmann²

2008

Cytokine & Growth Factor Reviews

153

117

View full text Add to dashboard Cite

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“…RelB is known to facilitate the development of DCs (Burkly et al, 1995;Weih et al, 1995); specifically development of CD8a À , but not CD8a þ , DCs (Wu et al, 1998). Conversely, double knockout studies have shown that canonical p50/RelA complexes are required for the development of both CD8a þ and CD8a À DCs, but not other myeloid and lymphoid lineages, most likely by mediating the response of DCs to TNFa (Ouaaz et al, 2002;Abe et al, 2003). Survival of DCs in the periphery following activation tends to be short, but can be prolonged upon CD40L expression on T cells.…”

Section: Nf-kb and Hematopoiesismentioning

confidence: 99%

“…Survival of DCs in the periphery following activation tends to be short, but can be prolonged upon CD40L expression on T cells. CD40L activates both the canonical and non-canonical NF-kB pathways and hence DCs deficient in both p50 and c-Rel, or DCs overexpressing a mutant super-repressor form of IkBa, demonstrate significantly decreased survival (Ouaaz et al, 2002;Kriehuber et al, 2005).…”

Section: Nf-kb and Hematopoiesismentioning

confidence: 99%

NF-κB and the immune response

2006

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“…Due to the opposite role of ERK1,2 and NF-κB signaling on DC maturation [23,24], we next evaluated the effects of MGL activation on phenotype and functions of DCs. We studied the expression of several DC markers after MGL binding, comparing the results with those obtained with iDCs or IgG 1 -DCs (Fig.…”

Section: Dcs Matured After Mgl Activationmentioning

confidence: 99%

Targeting of macrophage galactose‐type C‐type lectin (MGL) induces DC signaling and activation

et al. 2012

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Dendritic cells (DCs) sense the microenvironment through several types of receptors recognizing pathogen-associated molecular patterns. In particular, C-type lectins, expressed by distinct subsets of DCs, recognize and internalize specific carbohydrate antigen in a Ca 2+ -dependent manner. Targeting of these receptors is becoming an efficient strategy of delivering antigens in DC-based anticancer immunotherapy. Here we investigated the role of the macrophage galactose type C-lectin receptor (MGL), expressed by immature DCs (iDCs), as a molecular target for α-N-acetylgalactosamine (GalNAc or Tn)-carrying tumor-associated antigens to improve DC performance. MGL expressed by ex vivo-generated iDCs from healthy donors was engaged by a 60-mer MUC1 9Tn -glycopeptide as a Tn-carrying tumor-associated antigen, and an anti-MGL antibody, as a specific MGL binder. We demonstrated that MGL engagement induced homotrimers and homodimers, triggering the phosphorylation of extracellular signal-regulated kinase 1,2 (ERK1,2) and nuclear factor-κB activation. Analysis of DC phenotype and function demonstrated that MGL engagement improved DC performance as antigen-presenting cells, promoting the upregulation of maturation markers, a decrease in phagocytosis, an enhancement of motility, and most importantly an increase in antigen-specific CD8 + T-cell activation. These results demonstrate that the targeting of MGL receptor on human DCs has an adjuvant effect and that this strategy can be used to design novel anticancer vaccines. Keywords: C-type lectins · Dendritic cells · Macrophage galactose-type C-type lectin (MGL) · MUC1 · Tn-tumor associated antigens IntroductionDendritic cells (DCs), as professional antigen-presenting cells (APCs), sense the microenvironment through different types of Correspondence: Prof. Marianna Nuti e-mail: marianna.nuti@uniroma1.it receptors to scan local environmental changes and eliminate incoming pathogens [1]. They play an essential role in the uptake of self-or pathogen-associated antigens, thus, steering and directing the immune response. After activation, DCs migrate to the draining lymph nodes, where they initiate specific immunity * These authors contributed equally to this work. The most important molecules from the CLR family include macrophage galactose type C-lectin (MGL), dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), the mannose receptor, DEC205, and Dectin-1. These receptors are able to trigger distinct signaling pathways that modulate DC functions through the expression of specific molecules and cytokines, determining the polarization of T cells [4]. These properties make this C-type lectin family an optimal tool for DC targeting in cancer vaccination. Human MGL (hMGL) is a type II C-type lectin, expressed in vitro by macrophages and monocyte derived DCs and in vivo by DCs of skin and lymph nodes [5,6]. Its carbohydrate recognition domains contain a QPD sequence that is responsible for recognition of α-or β-N-acetylgalactosamine (GalNAc, Tn) res...

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Dendritic Cell Development and Survival Require Distinct NF-κB Subunits

Cited by 357 publications

References 51 publications

Crosstalk via the NF-κB signaling system

Crosstalk via the NF-κB signaling system

NF-κB and the immune response

Targeting of macrophage galactose‐type C‐type lectin (MGL) induces DC signaling and activation

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