There is an established consensus that it is primarily the adaptive arm of immunity, and the T cell subset in particular, that is most susceptible to the deleterious changes with age known as "immunosenescence". Can we garner any clues as to why this might be by considering comparative immunology and ...

Recent years have witnessed a renaissance in the study of fish immune systems. Such studies have greatly expanded the knowledge of the evolution and diversification of vertebrate immune systems. Several findings in those studies have overturned old paradigms about the immune system and led to the discovery of novel aspects ...

Much is now known about the vertebrate mechanisms involved in mucosal immunity, and the requirement of commensal microbiota at mucosal surfaces for the proper functioning of the immune system. In comparison, very little is known about the mechanisms of immunity at the barrier epithelia of non-vertebrate organisms. The purpose of ...

An alternative adaptive-immune system is present in the most basal vertebrates-lampreys and hagfish-the only surviving jawless vertebrates. These eel-like fish use leucine-rich repeat-based receptors for Ag recognition instead of the Ig-based receptors used in jawed vertebrates. We report that in Japanese lamprey (Lampetra japonica), variable lymphocyte receptor (VLR)B interacts with ...

The discovery of the key role of Toll-like receptors (TLRs) in initiating innate immune responses and modulating adaptive immunity has revolutionized our understanding of vertebrate defence against pathogens. Yet, despite their central role in pathogen recognition and defence initiation, there is little information on how variation in TLRs influences disease ...

Lampreys, the surviving representative of jawless vertebrates, have been a focal point in the search for the evolutionary origin of adaptive immunity. They have independently evolved the variable lymphocyte receptor (VLR)-based adaptive immune system that protects themselves from infection by a variable of microorganisms. The standard immunization schedule for Japanese ...

In the immune system of vertebrates, gender-specific differences in individual immune competence are well known. In general, females possess more powerful immune response than males. In invertebrates, the situation is much less clear. For this purpose we have chosen to study the immune response of the two sexes of the ...

Toll-like receptor (TLR) signaling is one of the most important signaling cascades of the innate immune system of vertebrates. Studies in invertebrates have focused on the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans, and there is little information regarding the evolutionary origin and ancestral function of TLR signaling. ...

To maintain homeostasis the animal body is equipped with a powerful system to remove circulating waste . This review presents evidence that the scavenger endothelial cell (SEC) is responsible for the clearance of blood-borne waste macromolecules in vertebrates. SECs express pattern-recognition endocytosis receptors (mannose and scavenger receptors), and in mammals, ...

Animals must manage interactions with beneficial as well as detrimental microbes. Immunity therefore includes strategies for both resistance to and tolerance of microbial invaders. Transforming growth factor beta (TGFβ) cytokines have many functions in animals including a tolerance-promoting (tolerogenic) role in immunity in vertebrates. TGFβ pathways are present in basal ...

The emergence of the adaptive immune system in vertebrates set the stage for evolution of an advanced symbiotic relationship with the intestinal microbiota. The defining features of specificity and memory that characterize adaptive immunity have afforded vertebrates the mechanisms for efficiently tailoring immune responses to diverse types of microbes, whether ...

Because jawless vertebrates are the most primitive vertebrates, they have been studied to understand the evolutionary processes that gave rise to the innate and adaptive immune systems in vertebrates. The jawless vertebrates have developed lymphocyte-like cells (LLCs) that morphologically resemble the T and B cells of jawed vertebrates, but they ...

[This corrects the article on p. e39888 in vol. 7.].

[This corrects the article on p. e34843 in vol. 7.].

Cannabis extracts and several cannabinoids have been shown to exert broad anti-inflammatory activities in experimental models of inflammatory CNS degenerative diseases. Clinical use of many cannabinoids is limited by their psychotropic effects. However, phytocannabinoids like cannabidiol (CBD), devoid of psychoactive activity, are, potentially, safe and effective alternatives for alleviating neuroinflammation ...

It has recently been suggested that, rather than being an autoimmune disease, multiple sclerosis (MS) is an example of a neurocristopathy, a pathological process resulting from a faulty development of the neural crest. Whilst several characteristics of the disease suggest a neurocristopathy, other aetiological factors require consideration, including hygiene-related factors ...

The presence of the blood-brain barrier (BBB) restricts the movement of soluble mediators and leukocytes from the periphery to the central nervous system (CNS). Leukocyte entry into the CNS is nonetheless an early event in multiple sclerosis (MS), an inflammatory disorder of the CNS. Whether BBB dysfunction precedes immune cell ...

Until recently, all approved multiple sclerosis (MS) disease treatments were administered parenterally. Oral fingolimod was approved in September 2010 by the US Food and Drug Administration to reduce relapses and disability progression in relapsing forms of MS. In the clinical trials that led to approval, fingolimod reduced not only acute ...

This review explores the principle features of the immunopathology of multiple sclerosis (MS), particularly relapsing-remitting MS. It highlights the emerging concepts in the pathogenesis of MS in the context of known features of pathology, including the characterization of cytokine networks promoting inflammatory damage of the central nervous system, B-cell involvement, ...

Vasectomy is a well accepted global contraceptive approach frequently associated with epididymal granuloma and sperm autoantibody formation. To understand the long-term sequelae of vasectomy, we investigated the early immune response in vasectomized mice. Vasectomy leads to rapid epithelial cell apoptosis and necrosis, persistent inflammation, and sperm granuloma formation in the ...

An acidic polysaccharide of Panax ginseng (APG), so called ginsan, is a purified polysaccharide. APG has multiple immunomodulatory effects of stimulating natural killer (NK) and T cells and producing a variety of cytokines that proved to diminish the proinflammatory response, and protect from septic lethality. To determine APG's role in ...

Natalizumab is a widely accepted drug for the relapsing-remitting subtype of multiple sclerosis (RRMS). The present longitudinal exploratory study in RRMS patients analyzes the effects of natalizumab treatment on the levels of pro-inflammatory and anti-inflammatory cytokine protein levels and also the frequency and suppressor function of regulatory T cells. Flow ...

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is widely used to dissect molecular mechanisms of MS and to develop new therapeutic strategies. The T helper 17 (Th17) subset of CD4 T cells plays a crucial role in the ...

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), characterized by inflammation, demyelination and axonal loss underlying progressive clinical disability. The chronic inflammatory tissue damage involving myelin and axons is driven by autoreactive T cells and represents a key mechanism in the immunopathogenesis of MS. Over ...

Autoantibodies constitute the hallmark of antineutrophil cytoplasmic antibody-associated vasculitis (AAV); however, CD4+ T cells play an essential role in the development of autoimmunity. Infection is associated with vasculitis, with Toll-like receptors (TLRs) a potential link between infection and autoimmunity. This study was undertaken to investigate the role of TLR ligation ...

Astrocytes are the most abundant cell population within the CNS of mammals. Their glial role is perfectly performed in the healthy CNS as they support functions of neurons. The omnipresence of astrocytes throughout the white and grey matter and their intimate relation with blood vessels of the CNS, as well ...

Foxp3(+) T-regulatory cells (Tregs) are key to immune homeostasis such that their diminished numbers or function can cause autoimmunity and allograft rejection. Foxp3(+) Tregs express multiple histone/protein deacetylases (HDACs) that regulate chromatin remodeling, gene expression, and protein function. Pan-HDAC inhibitors developed for oncologic applications enhance Treg production and Treg suppression ...

The organometallic glutathione S-transferase inhibitor ruthenium(II) (ethacrynic acid-η(6)-benzylamide)(1,3,5-triaza-7-phosphaadamantane) dichloride, termed ethaRAPTA, has been demonstrated to induce apoptosis in the cisplatin-resistant MCF-7 breast cancer cell line. Probing the molecular basis of this activity suggests that the complex triggers multiple pathways toward apoptosis, including those involving endonuclease G, caspases, and c-Jun N-terminal kinase, ...

Multiple sclerosis (MS) is a progressive neurodegenerative disease affecting myelin and axons, which is perpetuated by autoreactive lymphocytes and other inflammatory cell types. Because of the multifactorial nature of this disease, therapies targeting a single process may not be sufficient to halt its progression. VIP and PACAP are two neuropeptides ...

Laquinimod is a novel, orally administered immune-modulatory molecule in advanced phase clinical trials in relapsing-remitting multiple sclerosis. Experimental evidence to date, derived mostly from animal models of multiple sclerosis, suggests that laquinimod may mediate its effects via modulating pro-inflammatory immune responses and interfering with cell trafficking, as well as potentially ...

Multiple sclerosis is a debilitating disease of the central nervous system that has been characteristically classified as an immune-mediated destruction of myelin, the protective coating on nerve fibers. Although the mechanisms responsible for the immune attack to central nervous system myelin have been the subject of intense investigation, more recent ...

T-bet was initially described as a T-box transcription factor with an essential role in orchestrating Th1 cell differentiation. Subsequently, it was determined that T-bet controls the expression of numerous cytokines and their receptors, adhesion molecules and chemokine receptors, and therefore determines the differentiation and development status of many types of ...

Although inhibitors of histone deacetylase inhibitors (HDACis) in combination with genotoxins potentiate apoptosis, the role of proteases other than caspases in this process remained elusive. Therefore, we examined the potentiation of apoptosis and related mechanisms of HDACis and doxorubicin combination in a panel of myeloma cell lines and in 25 ...

Multiple sclerosis is an inflammatory and degenerative disease of the central nervous system characterized by demyelination and axonal loss. Genetic and environmental factors contribute to the risk of immune dysregulation in multiple sclerosis. The review focuses on the immunopathogenic role played by various lymphocyte subsets and their cytokine products in ...

Abstract Objective: Metabolic syndrome (MS) is a cluster of metabolic abnormalities associated with obesity, insulin resistance (IR), dyslipidemia, and hypertension in which inflammation plays an important role. Few studies have addressed the role played by T cell-derived cytokines in MS. The aim of the study was to look at the ...

At present, a series of oral disease-modifying agents is being introduced for the treatment of multiple sclerosis. With the exception of laquinimod, the "new" oral compounds have already been approved for other indications such as organ transplantation (FTY720), psoriasis (dimethylfumarate), hairy cell leukemia (cladribine), and rheumatoid arthritis (leflunomide). Leflunomide is ...

In multiple sclerosis, long-term disability is caused by axonal and neuronal damage. Established therapies target primarily the inflammatory component of the disease, but fail to prevent neurodegeneration. Fingolimod (codenamed FTY720) is an oral sphingosine 1-phosphate (S1P) receptor modulator with promising results in phase II trials in multiple sclerosis patients and ...

Fumaric acid was originally therapeutically used in psoriasis. Several lines of evidence have demonstrated immunomodulatory but also neuroprotective effects for FAE. Clinical studies in psoriasis showed a reduction of peripheral CD4+ and CD8+ T-lymphocytes due to the ability of FAE to induce apoptosis. In vitro studies with the ester dimethylfumarate ...

Type I interferon (IFN) is a common therapy for autoimmune and inflammatory disorders, yet the mechanisms of action are largely unknown. Here we showed that type I IFN inhibited interleukin-1 (IL-1) production through two distinct mechanisms. Type I IFN signaling, via the STAT1 transcription factor, repressed the activity of the ...

Multiple sclerosis (MS) is a devastating autoimmune disorder of the CNS for which there is no efficacious cure. Thanks to the numerous preclinical and clinical studies, drugs able to mitigate the inexorable course of the disease have been recently made available. Still, there is terrible need for compounds capable of ...

Multiple sclerosis (MS) is the most common acquired inflammatory demyelinating disorder of the central nervous system (CNS). Not unlike many inflammatory diseases with a presumed autoimmune pathogenesis, it has been established that there is a female preponderance in prevalence. While in the past it was shown that there are two ...

Abnormal aggregates of transactive response DNA-binding protein-43 (TDP-43) and its hyperphosphorylated and N-terminal truncated C-terminal fragments (CTFs) are deposited as major components of ubiquitinated inclusions in most cases of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U). The mechanism underlying the contribution of TDP-43 to the ...

Multiple sclerosis (MS) is an autoimmune disease characterized by recurrent episodes of demyelination and axonal lesion mediated by CD4(+) T cells with a proinflammatory Th1 and Th17 phenotype, macrophages, and soluble inflammatory mediators. Identification of Th17 cells led to breaking the dichotomy of Th1/Th2 axis in immunopathogenesis of autoimmune diseases ...

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune inflammation of the central nervous system and is used as the experimental model of multiple sclerosis (MS). The exact mechanism behind the disease is still unknown, but interleukin (IL)-17 expressing T cells are thought to mediate the disease. Toll-like receptors (TLRs) are known ...

Chronic inflammation contributes to numerous diseases, and regulation of inflammation is crucial for disease control and resolution. Sex hormones have potent immunoregulatory abilities. Specifically, estrogen influences immune cells and inflammation, which contributes to the sexual dimorphism of autoimmunity and protection against disease seen during pregnancy in multiple sclerosis (MS) and ...

Neuronal or photoreceptor deficit observed in uveitis and multiple sclerosis derives in part from inability to control inflammatory responses in neuroretina or brain. Recently, IL-27 was found to play a role in suppressing experimental autoimmune uveitis and experimental autoimmune encephalomyelitis, two animal models that share essential pathological features of human ...

Theiler's virus (TMEV) infection of the central nervous system (CNS) induces an immune-mediated demyelinating disease in susceptible mouse strains and serves as a relevant infection model for human multiple sclerosis (MS). The endocannabinoid system represents a novel therapeutic target for autoimmune and chronic inflammatory diseases due to its anti-inflammatory properties ...

Viral components can trigger autoimmunity, but the involved mechanisms remain to be elucidated. Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA (dsRNA) and appears to play an important role in this context. Our previous studies showed that signaling of TLR2, TLR3, TLR4 and TLR9 is highly redundant in the adjuvant ...

Microbial pathogens cause widespread morbidity and mortality. Central to the pathogens' virulence is manipulation of the host cell's cytoskeleton, which facilitates microbial invasion, multiplication, and avoidance of the innate immune response. IQGAP1 is a ubiquitously expressed scaffold protein that integrates diverse signaling cascades. Research has shown that IQGAP1 binds to ...

CD4(+) T-cell (Th) cytokines provide important regulatory and effector functions of T-cells. Among them, IL-2 plays a unique role. IL-2 is required for the generation and maintenance of regulatory T-cells (Treg) to provide lifelong protection from autoimmune disease. Whether IL-2 is also required for autoimmune disease development is less clear ...