Search results for "Autoimmune"
showing 10 items of 648 documents
IL-17 and related cytokines involved in the pathology and immunotherapy of multiple sclerosis: Current and future developments.
2014
Multiple sclerosis (MS), an autoimmune neurological disorder, is driven by self-reactive T helper (Th) cells. Research on the role of Th17 lymphocytes in MS pathogenesis has made significant progress in identifying various immunological as well as environmental factors that induce the differentiation and expansion of these cells, different subsets of Th17 cells with varying degrees of pathogenicity, and the role of the secreted effector cytokines. While approved therapies for MS offer significant benefit to patients, there remain unmet needs. Ongoing clinical trials aim to translate the advanced knowledge of Th17 cytokines to improved therapies. This review discusses the current status and …
Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma.
2021
Getting around the blood–brain barrier The meninges comprise three membranes that surround and protect the central nervous system (CNS). Recent studies have noted the existence of myeloid cells resident there, but little is known about their ontogeny and function, and whether other meningeal immune cell populations have important roles remains unclear (see the Perspective by Nguyen and Kubes). Cugurra et al. found in mice that a large proportion of continuously replenished myeloid cells in the dura mater are not blood derived, but rather transit from cranial bone marrow through specialized channels. In models of CNS injury and neuroinflammation, the authors demonstrated that these myeloid c…
Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient KitW-sh/W-sh mice
2011
Mast cell (MC)-deficient c-Kit mutant Kit(W/W-v) mice are protected against experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, suggesting a detrimental role for MCs in this disease. To further investigate the role of MCs in EAE, we took advantage of a recently characterized model of MC deficiency, Kit(W-sh/W-sh). Surprisingly, we observed that myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced chronic EAE was exacerbated in Kit(W-sh/W-sh) compared with Kit(+/+) mice. Kit(W-sh/W-sh) mice showed more inflammatory foci in the central nervous system (CNS) and increased T-cell response against myelin. To understand whether the discrepant results obtaine…
Elevated NKG2D ligand expression in experimental autoimmune encephalomyelitis
2014
T cells remain unclear. Expressing myelin-reactive T cell receptor (TCR) is not sufficient to make a T cell encephalitogenic. In fact, the frequencies of myelin-reactive T cells are comparable between MS patients and healthy individuals, but the ones in MS patients have activated/memory phenotypes. In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), myelin-specific T cells activated with antigen presenting cells (APCs) plus myelin peptide are encephalitogenic, whereas T cells activated with anti-CD3/CD28 antibodies are not. This suggests that APCs provide critical cytokines beyond T cell receptor activation and co-stimulation, contributing to encephalitogenicity. To …
The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis.
2019
Th17 cells, known as a highly pro-inflammatory subtype of Th cells, are involved very early in numerous aspects of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) neuropathology. A crucial event for the formation and accumulation of MS lesions is represented by the disruption of the blood brain barrier (BBB) in relapsing-remitting MS. Th17 cells also contribute to the progression of MS/EAE. These events will allow for the passage of inflammatory cells into the brain. Secondary to this, increased recruitment of neutrophils occurs, followed by increased protease activity that will continue to attract macrophages and monocytes, leading to brain inflammation with sus…
The fungal lactone oxacyclododecindione is a potential new therapeutic substance in the treatment of lupus-associated kidney disease.
2013
Recently oxacyclododecindione (Oxa), a macrocyclic lactone isolated from the imperfect fungus Exserohilum rostratum, has been described as a potent transcription inhibitor of inducible proinflammatory and profibrotic genes in cell culture models. As kidney disease in systemic lupus erythematosus is characterized by aberrant expression of inflammatory mediators and infiltration of immune cells, we investigated the effect of Oxa in MRL-Fas(lpr) mice, a model of systemic lupus erythematosus. These mice develop a spontaneous T-cell and macrophage-dependent autoimmune disease including severe glomerulonephritis that shares features with human lupus. Comparable to the results of in vitro models, …
Cholera-Like Enterotoxins and Regulatory T cells
2010
Cholera toxin (CT) and the heat-labile enterotoxin of E. coli (LT), as well as their non toxic mutants, are potent mucosal adjuvants of immunization eliciting mucosal and systemic responses against unrelated co-administered antigens in experimental models and in humans (non toxic mutants). These enterotoxins are composed of two subunits, the A subunit, responsible for an ADP-ribosyl transferase activity and the B subunit, responsible for cell binding. Paradoxically, whereas the whole toxins have adjuvant properties, the B subunits of CT (CTB) and of LT (LTB) have been shown to induce antigen specific tolerance when administered mucosally with antigens in experimental models as well as, rece…
Dependence on nuclear factor of activated T-cells (NFAT) levels discriminates conventional T cells from Foxp3 + regulatory T cells
2012
Several lines of evidence suggest nuclear factor of activated T-cells (NFAT) to control regulatory T cells: thymus-derived naturally occurring regulatory T cells (nTreg) depend on calcium signals, the Foxp3 gene harbors several NFAT binding sites, and the Foxp3 (Fork head box P3) protein interacts with NFAT. Therefore, we investigated the impact of NFAT on Foxp3 expression. Indeed, the generation of peripherally induced Treg (iTreg) by TGF-β was highly dependent on NFAT expression because the ability of CD4 + T cells to differentiate into iTreg diminished markedly with the number of NFAT family members missing. It can be concluded that the expression of Foxp3 in TGF-β–induced iTreg depends…
Interferon alfa–induced sarcoidosis resolving without drug withdrawal
2016
Sarcoidosis is an uncommon systemic granulomatous disease of unknown origin affecting lung, skin, liver, and other tissues. Noncaseating granulomas in the involved organs are the hallmark of this disease. An exaggerated immune response to an unknown antigenic stimulus could play a role in sarcoidosis development. Lung is one of the most frequently involved organs.1 Manifestations range from alveolitis to granulomatous infiltration of alveoli, bronchi, and blood vessels. The end stage of lung sarcoidosis is development of interstitial fibrosis with “honeycombing” of lung parenchyma. Interferon alfa in association with ribavirin is the treatment of choice for hepatitis C. Early treatment of a…
NFAT transcription factors in control of peripheral T cell tolerance.
2006
The Ca++-regulated calcineurin/NFAT cascade is one of the crucial signalling pathways that controls adaptive immunity. However, a number of novel experimental data suggest that, in addition to their role in T cell activation, NFATc transcription factors play also a decisive role in the generation of peripheral tolerance against self-antigens. This function of NFATc factors is mediated by controlling activation-induced cell death and clonal anergy of T helper cells and the activity of regulatory T cells. The multi-functional role of NFATc proteins characterize these transcription factors as key regulators of immunological tolerance and, if dysregulated, of development of autoimmune diseases.