Search results for "IMMUNOLOGY"
showing 10 items of 9651 documents
SPARC regulation of PMN clearance protects from pristane-induced lupus and rheumatoid arthritis
2021
Summary The secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein with unexpected immunosuppressive function in myeloid cells. We investigated the role of SPARC in autoimmunity using the pristane-induced model of lupus that, in mice, mimics human systemic lupus erythematosus (SLE). Sparc−/− mice developed earlier and more severe renal disease, multi-organ parenchymal damage, and arthritis than the wild-type counterpart. Sparc+/- heterozygous mice showed an intermediate phenotype suggesting Sparc gene dosage in autoimmune-related events. Mechanistically, reduced Sparc expression in neutrophils blocks their clearance by macrophages, through defective delivery of don'…
Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation
2016
Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation. In epidermis and dermis, the critical DCs are TNF-producing and IL-1β-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. Depleting Ly6Chi blood monocytes reduces DC accumulation and the skin changes induced either by injecting IL-23 or by application of the TLR7 agonist imiquimod. Moreover, we find that IL-23-…
Gene expression changes after parental exposure to metals in the sea urchin affect timing of genetic programme of embryo development
2021
Simple Summary Intergenerational and transgenerational effects, in which exposure to stressors in a parental generation affects the phenotype of the offspring have been connected to anthropic impacts on biological systems. Therefore, environmental stress experienced inside a generation, particularly during gametogenesis, may lead to erroneous patterns in their offspring just emerging at early developmental stages. In this scenario, the sea urchin embryo represents a suitable model for integrating analyses of gene expression through embryogenesis with developmental alteration induced by environmental stressors. Herein we provide pieces of evidence for the alteration of the gene regulatory ne…
Resistance against Echinostoma caproni (Trematoda) secondary infections in mice is not dependent on the ileal protein production
2016
Echinostoma caproni (Trematoda: Echinostomatidae) is an intestinal trematode, which has been widely employed to investigate the factors determining the rejection of intestinal helminths. Protein production patterns of intestinal epithelial cells are related to the infection-induced changes that determine the course of E. caproni infections. Herein, we compare the protein production profiles in the ileum of four experimental groups of mice: control; infected; dewormed and reinfected. Worm burdens were significantly lower in secondary infections, confirming the generation of partial resistance to homologous secondary infections in mice. However, quantitative comparison by 2D-DIGE showed that …
p53 and p53-related mediators PAI-1 and IGFBP-3 are downregulated in peripheral blood mononuclear cells of HIV-patients exposed to non-nucleoside rev…
2019
The improved effectiveness and safety of the combined antiretroviral therapy (cART) has largely diminished mortality and AIDS-defining morbidity of HIV-patients. Nevertheless, chronic age-related diseases in these individuals are more common and their underlying pathogenic mechanisms of these actions seem to involve accelerated aging and enhanced inflammation. The present study explores markers of these processes in a heterogenous Spanish HIV cohort using peripheral blood samples of HIV-patients and matched uninfected controls. We isolated periheral blood mononuclear cells (PBMCs) and i) compared the expression of a panel of 14 genes related to inflammation and senescence in PBMCs of HIV-pa…
Vascular ageing and endothelial cell senescence: Molecular mechanisms of physiology and diseases
2016
Ageing leads to a progressive deterioration of structure and function of all organs over the time. During this process endothelial cells undergo senescence and manifest significant changes in their properties, resulting in impairment of the vascular functionality and neo-angiogenic capability. This ageing-dependent impairment of endothelial functions is considered a key factor contributing to vascular dysfunctions, which is responsible of several age-related diseases of the vascular system and other organs. Several mechanisms have been described to control ageing-related endothelial cell senescence including microRNAs, mitochondrial dysfunction and micro environmental stressors, such as hyp…
Gut microbiota and aging-A focus on centenarians.
2020
Gut microbiota (GM) is a dynamic organ throughout the lifespan. Aging is a complex process that comprises a plethora of mechanisms such as senescence, immunosenescence and inflammaging, representing important pathways of age-related diseases. GM structure could both influence and be influenced by aging occurring changes within the host. A unique category of long living individuals exists, namely centenarians that have the outstanding capacity to adapt to various challenges. Longevity seems to be associated with certain GM which, among other factors, might render individuals more resistant to age-related diseases and subsequently to long living. Diet, prebiotics, probiotics and synbiotics ma…
Chemotherapy accelerates immune-senescence and functional impairments of Vδ2pos T cells in elderly patients affected by liver metastatic colorectal c…
2019
Abstract Human (gamma delta) γδ T cells are unconventional innate-like lymphocytes displaying a broad array of anti-tumor activities with promising perspectives in cancer immunotherapy. In this context, Vδ2pos T cells represent the preferential target of several immunotherapy protocols against solid tumors. However, the impact of both aging and chemotherapy (CHT) on Vδ2pos T cells is still unknown. The present study evaluates with multi-parametric flow cytometry the frequencies, terminal differentiation, senescence and effector-functions of peripheral blood and tumor infiltrating Vδ2pos T cells purified from liver metastases (CLM) of patients affected by colorectal cancer (CRC) compared to …
Induction of dormancy in hypoxic human papillomavirus-positive cancer cells
2017
Oncogenic human papillomaviruses (HPVs) are closely linked to major human malignancies, including cervical and head and neck cancers. It is widely assumed that HPV-positive cancer cells are under selection pressure to continuously express the viral E6/E7 oncogenes, that their intracellular p53 levels are reconstituted on E6/E7 repression, and that E6/E7 inhibition phenotypically results in cellular senescence. Here we show that hypoxic conditions, as are often found in subregions of cervical and head and neck cancers, enable HPV-positive cancer cells to escape from these regulatory principles: E6/E7 is efficiently repressed, yet, p53 levels do not increase. Moreover, E6/E7 repression under …
Oxidative stress, autophagy, epigenetic changes and regulation by miRNAs as potential therapeutic targets in osteoarthritis
2015
Aging is a natural process characterized by the declining ability of the different organs and tissues to respond to stress, increasing homeostatic imbalance and risk of disease. Osteoarthritis (OA) is a multifactorial disease in which cartilage degradation is a central feature. Aging is the main risk factor for OA. In OA cartilage, a decrease in the number of chondrocytes and in their ability to regenerate the extracellular matrix and adequately respond to stress has been described. OA chondrocytes show a senescence secretory phenotype (SSP) consisting on the overproduction of cytokines (interleukins 1 and 6), growth factors (e.g., epidermal growth factor) and matrix metalloproteinases (MMP…