Interferon-<i>β</i>up-regulates the expression of co-stimulatory molecules CD80, CD86 and CD40 on monocytes: significance for treatment of multiple sclerosis

Marckmann, S.; Wiesemann, Elke; Hilse, R.; Trebst, Corinna; Stangel, Martin; Windhagen, Anja

doi:10.1111/j.1365-2249.2004.02624.x

Cited by 51 publications

(42 citation statements)

References 54 publications

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“…As described previously [19,22,43,44] CD40 and CD80 expressions on CD14 + monocytes were not detected in four of six and in five of six controls, respectively. In contrast, in monocytes from PBMC isolated from 10 patients immediately after surgery, CD40 and CD80 were expressed in seven and four patients, respectively, although this did not amount to statistically significant differences.…”

Section: Expression Of Cd40 Cd80 Tlr2 Tlr4 and Ccr7 On Monocytes Asupporting

confidence: 69%

Acceleratedin vitrodifferentiation of blood monocytes into dendritic cells in human sepsis

Faivre

Lukaszewicz

Alves

et al. 2007

Clinical and Experimental Immunology

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SummarySepsis-induced immune depression is characterized by infection susceptibility and monocyte early deactivation. Because monocytes are precursors for dendritic cells (DC), alterations in their differentiation into DC may contribute to defective immune responses in septic patients. We therefore investigated the ability of monocytes to differentiate into functional DC in vitro in patients undergoing surgery for peritonitis. Monocytes from 20 patients collected immediately after surgery (D0), at week 1 and at weeks 3-4 and from 11 control donors were differentiated into immature DC. We determined the phenotype of monocytes and derived DC, and analysed the ability of DC to respond to microbial products and to elicit T cell responses in a mixed leucocyte reaction (MLR). We show that, although monocytes from septic patients were deactivated with decreased responses to lipopolysaccharide (LPS) and peptidoglycan and low human leucocyte antigen D-related (HLA-DR) expression, they expressed the co-stimulatory molecule CD80, CD40 and CCR7. Monocytes collected from patients at D0 and week 1 differentiated faster into DC with early loss of CD14 expression. Expression of HLA-DR increased dramatically in culture to reach control levels, as did responses of DC to LPS and peptidoglycan. However, although patient and control immature DC had similar abilities to induce T cell proliferation in MLR, maturation of DC derived from patients did not increase T cell responses. These results show that circulating monocytes from septic patients express markers of activation and/or differentiation despite functional deactivation, and differentiate rapidly into phenotypically normal DC. These DC fail, however, to increase their T cell activation abilities upon maturation.

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Section: Expression Of Cd40 Cd80 Tlr2 Tlr4 and Ccr7 On Monocytes Asupporting

confidence: 69%

Acceleratedin vitrodifferentiation of blood monocytes into dendritic cells in human sepsis

Faivre

Lukaszewicz

Alves

et al. 2007

Clinical and Experimental Immunology

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“…TLR ligand‐induced up‐regulation of co‐stimulatory molecules including B7‐1 depends on type I IFN signalling . Here we show that podocytes can recognize a variety of different TLR ligands and mount a type I IFN response that triggers actin remodelling and B7‐1 induction, thereby leading to proteinuria.…”

Section: Introductionmentioning

confidence: 79%

Inhibition of type I interferon signalling prevents TLR ligand-mediated proteinuria

et al. 2013

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The mechanisms by which inflammation or autoimmunity causes proteinuric kidney disease remain elusive. Yet proteinuria is a hallmark and a prognostic indicator of kidney disease, and also an independent risk factor for cardiovascular morbidity and mortality. Podocytes are an integral component of the kidney filtration barrier and podocyte injury leads to proteinuria. Here we show that podocytes, which receive signals from the vascular space including circulating antigens, constitutively express TLR1–6 and TLR8. We find that podocytes can respond to TLR ligands including staphylococcal enterotoxin B (SEB), poly I:C, or lipopolysaccharide (LPS) with pro-inflammatory cytokine release and activation of type I interferon (IFN) signalling. This in turn stimulates podocyte B7-1 expression and actin remodelling in vitro and transient proteinuria in vivo. Importantly, the treatment of mice with a type I IFN receptor-blocking antibody (Ab) prevents LPS-induced proteinuria. These results significantly extend our understanding of podocyte response to immune stimuli and reveal a novel mechanism for infection- or inflammation-induced transient proteinuria. Dysregulation or aberrant activation of this response may result in persistent proteinuria and progressive glomerular disease. In summary, the inhibition of glomerular type I IFN signalling with anti-IFN Abs may be a novel therapy for proteinuric kidney diseases.

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“…Several studies demonstrated that keratinocytes in the viable epidermis produced various cytokines that were released into the surrounding environment when skin was exposed to physical stimuli associated with barrier disruption. 44,[49][50][51] Therefore, physical stimuli to the skin may induce the release of immune cytokines from living cells such as keratinocytes and sustainably affect the activation of LCs and dDCs in an indirect manner.…”

Section: Discussionmentioning

confidence: 99%

Application of Microneedles to Skin Induces Activation of Epidermal Langerhans Cells and Dermal Dendritic Cells in Mice

Takeuchi

Nomoto

Watanabe

et al. 2016

Biological & Pharmaceutical Bulletin

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An adequate immune response to percutaneous vaccine application is generated by delivery of sufficient amounts of antigen to skin and by administration of toxin adjuvants or invasive skin abrasion that leads to an adjuvant effect. Microneedles penetrate the stratum corneum, the outermost layer of the skin, and enable direct delivery of vaccines from the surface into the skin, where immunocompetent dendritic cells are densely distributed. However, whether the application of microneedles to the skin activates antigen-presenting cells (APCs) has not been demonstrated. Here we aimed to demonstrate that microneedles may act as a potent physical adjuvant for successful transcutaneous immunization (TCI). We prepared samples of isolated epidermal and dermal cells and analyzed the expression of major histocompatibility complex (MHC) class II and costimulatory molecules on Langerhans or dermal dendritic cells in the prepared samples using flow cytometry. The expression of MHC class II and costimulatory molecules demonstrated an upward trend in APCs in the skin after the application of 500-and 300-µm microneedles. In addition, in the epidermal cells, application of microneedles induced more effective activation of Langerhans cells than did an invasive tapestripping (positive control). In conclusion, the use of microneedles is likely to have a positive effect not only as an antigen delivery system but also as a physical technique inducing an adjuvant-like effect for TCI.

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Interferon-βup-regulates the expression of co-stimulatory molecules CD80, CD86 and CD40 on monocytes: significance for treatment of multiple sclerosis

Cited by 51 publications

References 54 publications

Acceleratedin vitrodifferentiation of blood monocytes into dendritic cells in human sepsis

Acceleratedin vitrodifferentiation of blood monocytes into dendritic cells in human sepsis

Inhibition of type I interferon signalling prevents TLR ligand-mediated proteinuria

Application of Microneedles to Skin Induces Activation of Epidermal Langerhans Cells and Dermal Dendritic Cells in Mice

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