Search results for "auto"

2019

Glaucoma is an optic neurological disorder and the leading cause of irreversible blindness worldwide, with primary open angle glaucoma (POAG) as its most prevalent form. An early diagnosis of the disease is crucial to prevent loss of vision. Mechanisms behind glaucoma pathogenesis are not completely understood, but disease related alterations in the serological autoantibody profile indicate an immunologic component. These changes in immunoreactivity may serve as potential biomarkers for glaucoma diagnostics. We aimed to identify novel disease related autoantibodies targeting antigens in the trabecular meshwork as biomarkers to support early detection of POAG. We used serological proteome an…

The janus face of NKT cell function in autoimmunity and infectious diseases

2018

Natural killer T cells (NKT) are a subset of T lymphocytes bridging innate and adaptive immunity. These cells recognize self and microbial glycolipids bound to non-polymorphic and highly conserved CD1d molecules. Three NKT cell subsets, type I, II and NKT-like expressing different antigen receptors (TCR) were described and TCR activation promotes intracellular events leading to specific functional activities. NKT can exhibit different functions depending on the secretion of soluble molecules and the interaction with other cell types. NKT cells act as regulatory cells in the defence against infections but, on the other hand, their effector functions can be involved in the pathogenesis of sev…

Association of interleukin-6 rs1800796 polymorphism with reduced cognitive performance in healthy older adults

2019

© 2018 Elsevier B.V. With increasing life expectancy, age-associated cognitive impairment is an escalating problem worldwide. Inflammation is one of the features that characterises cognitive decline and can stimulate neurodegeneration. Interleukin 6 (IL-6) is a cytokine frequently associated with a pro-inflammatory phenotype and increased levels have been associated with the pathogenesis of dementia. The rs1800796 polymorphism in the promoter region of IL-6 gene was previously shown to influence IL-6 expression and therefore we hypothesised this gene polymorphism would be associated with IL-6 plasma levels and cognitive performance of older adults. The present study investigated the associa…

Galectin-3 Released by Pancreatic Ductal Adenocarcinoma Suppresses γδ T Cell Proliferation but Not Their Cytotoxicity

2020

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an immunosuppressive tumor microenvironment with a dense desmoplastic stroma. The expression of β-galactoside-binding protein galectin-3 is regarded as an intrinsic tumor escape mechanism for inhibition of tumor-infiltrating T cell function. In this study, we demonstrated that galectin-3 is expressed by PDAC and by γδ or αβ T cells but is only released in small amounts by either cell population. Interestingly, large amounts of galectin-3 were released during the co-culture of allogeneic in vitro expanded or allogeneic or autologous resting T cells with PDAC cells. By focusing on the co-culture of tumor cells and γδ T cells, we obse…

Antigen specificity and clinical significance of IgG and IgA autoantibodies produced in situby tumor-infiltrating b cells in breast cancer

2018

An important role for tumor infiltrating B lymphocytes (TIL-B) in the immune response to cancer is emerging; however, very little is known about the antigen specificity of antibodies produced in situ. The presence of IgA antibodies in the tumor microenvironment has been noted although their biological functions and clinical significance are unknown. This study used a 91-antigen microarray to examine the IgG and IgA autoantibody repertoires in breast cancer (BC). Tumor and adjacent breast tissue supernatants and plasma from BC patients together with normal breast tissue supernatants and plasma from healthy controls (patients undergoing mammary reduction and healthy blood donors) were analyze…

The cAMP pathway as therapeutic target in autoimmune and inflammatory diseases

2016

Nucleotide signaling molecules contribute to the regulation of cellular pathways. In the immune system, cyclic adenosine monophosphate (cAMP) is well established as a potent regulator of innate and adaptive immune cell functions. Therapeutic strategies to interrupt or enhance cAMP generation or effects have immunoregulatory potential in autoimmune and inflammatory disorders. Here, we provide an overview of the cyclic AMP axis and its role as a regulator of immune functions and discuss the clinical and translational relevance of interventions with these processes.

RNase H2 Loss in Murine Astrocytes Results in Cellular Defects Reminiscent of Nucleic Acid-Mediated Autoinflammation

2018

Aicardi-Goutières syndrome (AGS) is a rare early onset childhood encephalopathy caused by persistent neuroinflammation of autoimmune origin. AGS is a genetic disorder and >50% of affected individuals bear hypomorphic mutations in ribonuclease H2 (RNase H2). All available RNase H2 mouse models so far fail to mimic the prominent CNS involvement seen in AGS. To establish a mouse model recapitulating the human disease, we deleted RNase H2 specifically in the brain, the most severely affected organ in AGS. Although RNase H2δGFAPmice lacked the nuclease in astrocytes and a majority of neurons, no disease signs were apparent in these animals. We additionally confirmed these results…

Peripherally Induced Regulatory T Cells: Recruited Protectors of the Central Nervous System against Autoimmune Neuroinflammation

2017

Defects in regulatory T cells (Treg cells) aggravate multiple sclerosis (MS) after its onset and the absence of Treg cell functions can also exacerbate the course of disease in an animal model of MS. However, autoimmune neuroinflammation in many MS models can be acutely provoked in healthy animals leading to an activation of encephalitogenic T cells despite the normal induction of immune tolerance in the thymus including thymically-produced (t)Treg cells. In contrast, neuroinflammation can be ameliorated or even completely prevented by the antigen-specific Treg cells formed extrathymically in the peripheral immune system (pTreg cells) during tolerogenic responses to relevant neuronal antige…

Editorial: Current concepts of cellular and biological drugs to modulate regulatory T cell activity in the clinic

2016

The Editorial on the Research Topic Current Concepts of Cellular and Biological Drugs to Modulate Regulatory T Cell Activity in the Clinic Regulatory T (Treg) cells are essential for the maintenance of peripheral tolerance and prevent the development of autoimmunity and allergy. While on the one hand being indispensable for the perpetuation of tolerance to harmless antigens or self-antigens, Treg cells contribute to cancer pathogenesis and progression (1). Hence, the potential to treat a multitude of different human diseases by pharmacological modulation of Treg cells is enormous. Consequently, this T cell population is in the focus of biomedical research and development. Currently, isolate…

Vγ9Vδ2 T Cells in the Bone Marrow of Myeloma Patients: A Paradigm of Microenvironment-Induced Immune Suppression

2018

Vγ9Vδ2 T cells are non-conventional T cells with a natural inclination to recognize and kill cancer cells. Malignant B cells, including myeloma cells, are privileged targets of Vγ9Vδ2 T cells in vitro. However, this inclination is often lost in vivo due to multiple mechanisms mediated by tumor cells and local microenvironment. Multiple myeloma (MM) is a paradigm disease in which antitumor immunity is selectively impaired at the tumor site. By interrogating the immune reactivity of bone marrow (BM) Vγ9Vδ2 T cells to phosphoantigens, we have revealed a very early and long-lasting impairment of Vγ9Vδ2 T-cell immune functions which is already detectable in monoclonal gammopathy of undetermined …