Search results for "Immunity"
showing 10 items of 1537 documents
Local delivery of mRNA-encoded cytokines promotes antitumor immunity and tumor eradication across multiple preclinical tumor models
2021
Local immunotherapy ideally stimulates immune responses against tumors while avoiding toxicities associated with systemic administration. Current strategies for tumor-targeted, gene-based delivery, however, are limited by adverse effects such as off-targeting or antivector immunity. We investigated the intratumoral administration of saline-formulated messenger (m)RNA encoding four cytokines that were identified as mediators of tumor regression across different tumor models: interleukin-12 (IL-12) single chain, interferon-α (IFN-α), granulocyte-macrophage colony-stimulating factor, and IL-15 sushi. Effective antitumor activity of these cytokines relied on multiple immune cell populations and…
Tumor vaccination using messenger RNA: prospects of a future therapy.
2011
While the endeavor to vaccinate against cancer has been pursued for over 20 years, only recently was the first tumor vaccine approved. Among the different antigen formats assessed for vaccination, coding messenger RNA (mRNA) is emerging as a particularly attractive option. It can code for all types of transcript based proteins, is easy and cost efficient to produce, has a favorable safety profile and enables induction of combined immune responses. Within the last few years major developments have been achieved in this field. Clinical approaches use mRNA either for direct administration or for engineering of adoptively transferred dendritic cells. However, there are still challenges to be ov…
Metal drugs and the anticancer immune response
2018
The immune system deploys a multitude of innate and adaptive mechanisms not only to ward off pathogens but also to prevent malignant transformation ("immune surveillance"). Hence, a clinically apparent tumor already reflects selection for those malignant cell clones capable of evading immune recognition ("immune evasion"). Metal drugs, besides their well-investigated cytotoxic anticancer effects, massively interact with the cancer-immune interface and can reverse important aspects of immune evasion. This topic has recently gained intense attention based on combination approaches with anticancer immunotherapy (e.g., immune checkpoint inhibitors), a strategy recently delivering first exciting…
Influence of heme oxygenase 1 modulation on the progression of murine collagen-induced arthritis.
2005
Contains fulltext : 48023.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Heme oxygenase 1 (HO-1) can be induced by inflammatory mediators as an adaptive response. The objective of the present study was to determine the consequences of HO-1 modulation in the murine collagen-induced arthritis (CIA) model. METHODS: DBA/1J mice were treated with an inhibitor of HO-1, tin protoporphyrin IX (SnPP), or with an inducer of HO-1, cobalt protoporphyrin IX (CoPP), from day 22 to day 29 after CIA induction. The clinical evolution of disease was monitored visually. At the end of the experiment, joints were examined for histopathologic changes. Cytokine levels in paws were measured by enzyme-linked…
MT5-MMP regulates adult neural stem cell functional quiescence through the cleavage of N-cadherin.
2014
The identification of mechanisms that maintain stem cell niche architecture and homeostasis is fundamental to our understanding of tissue renewal and repair. Cell adhesion is a well-characterized mechanism for developmental morphogenetic processes, but its contribution to the dynamic regulation of adult mammalian stem cell niches is still poorly defined. We show that N-cadherin-mediated anchorage of neural stem cells (NSCs) to ependymocytes in the adult murine subependymal zone modulates their quiescence. We further identify MT5-MMP as a membrane-type metalloproteinase responsible for the shedding of the N-cadherin ectodomain in this niche. MT5-MMP is co-expressed with N-cadherin in adult N…
Activation of the lectin pathway in murine lupus nephritis.
2004
In systemic lupus erythematosus (SLE), hypocomplementaemia and complement deposition have been described both in man and in experimental models. A major involvement of the classical pathway of complement activation has been demonstrated in this disease, however relatively little is known about the involvement of the lectin pathway. Therefore in the present study we have analyzed the activity of all three pathways of complement activation in murine models of SLE. In the mouse, MBL is expressed in two forms, namely MBL-A and MBL-C. In the present study young and old MRL-lpr and control MRL+/+ mice were compared for the levels of complement activity with specific attention for the lectin pathw…
Correlation of renal tubular epithelial cell-derived interleukin-18 up-regulation with disease activity in MRL-Faslpr mice with autoimmune lupus neph…
2002
Objective MRL-Faslpr mice spontaneously develop an autoimmune disease that mimics systemic lupus erythematosus in humans. Infiltrating T cells expressing interferon-γ (IFNγ) are responsible for the autoimmune kidney destruction in MRL-Faslpr mice, and interleukin-18 (IL-18) released by mononuclear phagocytes stimulates T cells to produce the IFNγ. Since MRL-Faslpr T cells are characterized by an overexpression of the IL-18 receptor accessory chain, we sought to determine the impact of IL-18 on the progression of lupus nephritis in MRL-Faslpr mice. Methods IL-18 expression in sera and kidney tissues from MRL-Faslpr mice was determined by enzyme-linked immunosorbent assay (ELISA), reverse tra…
β-Catenin in dendritic cells exerts opposite functions in cross-priming and maintenance of CD8+ T cells through regulation of IL-10
2015
Recent studies have demonstrated that β-catenin in DCs serves as a key mediator in promoting both CD4(+) and CD8(+) T-cell tolerance, although how β-catenin exerts its functions remains incompletely understood. Here we report that activation of β-catenin in DCs inhibits cross-priming of CD8(+) T cells by up-regulating mTOR-dependent IL-10, suggesting blocking β-catenin/mTOR/IL-10 signaling as a viable approach to augment CD8(+) T-cell immunity. However, vaccination of DC-β-catenin(-/-) (CD11c-specific deletion of β-catenin) mice surprisingly failed to protect them against tumor challenge. Further studies revealed that DC-β-catenin(-/-) mice were deficient in generating CD8(+) T-cell immunit…
Increase in gut microbiota after immune suppression in baculovirus-infected larvae.
2013
Spodoptera exigua microarray was used to determine genes differentially expressed in S. exigua cells challenged with the species-specific baculovirus SeMNPV as well as with a generalist baculovirus, AcMNPV. Microarray results revealed that, in contrast to the host transcriptional shut-off that is expected during baculovirus infection, S. exigua cells showed a balanced number of up- and down-regulated genes during the first 36 hours following the infection. Many immune-related genes, including pattern recognition proteins, genes involved in signalling and immune pathways as well as immune effectors and genes coding for proteins involved in the melanization cascade were found to be down-regul…
A case of visceral leishmaniasis and pulmonary tuberculosis in a post-partum woman
2015
AbstractVisceral leishmaniasis due to Leishmania infantum is a vector-borne zoonotic disease transmitted by sand fly bites endemic in rural or periurban areas of the Mediterranean basin. Pregnancy is accompanied by changes in immune response, mainly a decrease in cellular immunity and a proportional increase in humoral immunity. These physiological events result in increased risk of infection by pathogens whose immunity is based on a T-helper 1 predominant response. We describe a case of visceral leishmaniasis and pulmonary tuberculosis diagnosed in a post-partum woman four days after delivery. The diagnosis of leishmaniasis should be considered in pregnant women with fever and haematologic…