Search results for "Immune system"
showing 10 items of 2885 documents
Recombinant virus-like particles of a norovirus (genogroup II strain) administered intranasally and orally with mucosal adjuvants LT and LT(R192G) in…
2003
We investigated the immune response induced by mucosal immunization of BALB/c mice with virus-like particles (VLPs) of a genogroup II norovirus, Dijon171/96 virus, produced in the baculovirus system. VLPs administered alone by the intranasal route induced a high serum antibody response as well as fecal IgA, which were enhanced when the heat-labile Escherichia coli toxin or its non toxic mutant LT(R192G) was coadministered. In these conditions, the oral route was also efficient. Cytokine production by cells from different lymphoid tissues was then assessed after in vitro restimulation. A Th1/Th2-like response was observed in cervical lymph node and Peyer's patch (PP) cell cultures from mice …
Intrinsic TNFR2 signaling in T regulatory cells provides protection in CNS autoimmunity
2018
Significance In spite of TNF involvement in the pathogenesis of multiple sclerosis (MS), systemic TNF neutralization in MS patients was not successful. One of the possible reasons is that TNF possesses both pathogenic and protective features that may be related to TNFR1 versus TNFR2 receptor engagement. This study uncovers one of such protective functions of TNF mediated by intrinsic TNFR2 signaling in Treg cells. In mice bearing humanized TNF and TNFR2 genetic loci, TNFR2 ablation restricted to Treg cells led to reduced capacity to control Th17 cell responses, exacerbated experimental autoimmune encephalomyelitis (EAE) development, and affected the maintenance of Treg cells. These findings…
NF-κB inducing kinase (NIK) is an essential post-transcriptional regulator of T-cell activation affecting F-actin dynamics and TCR signaling
2018
NF-κB inducing kinase (NIK) is the key protein of the non-canonical NF-κB pathway and is important for the development of lymph nodes and other secondary immune organs. We elucidated the specific role of NIK in T cells using T-cell specific NIK-deficient (NIKΔT) mice. Despite showing normal development of lymphoid organs, NIKΔT mice were resistant to induction of CNS autoimmunity. T cells from NIKΔT mice were deficient in late priming, failed to up-regulate T-bet and to transmigrate into the CNS. Proteomic analysis of activated NIK-/- T cells showed de-regulated expression of proteins involved in the formation of the immunological synapse: in particular, proteins involved in cytoskeleton dy…
Microglia in CNS development: Shaping the brain for the future
2017
Microglial cells are the resident macrophages of the central nervous system (CNS) and are mainly known for their roles in neuropathologies. However, major recent developments have revealed that these immune cells actively interact with neurons in physiological conditions and can modulate the fate and functions of synapses. Originating from myeloid precursors born in the yolk sac, microglial cells invade the CNS during early embryonic development. As a consequence they can potentially influence neuronal proliferation, migration and differentiation as well as the formation and maturation of neuronal networks, thereby contributing to the entire shaping of the CNS. We review here recent evidenc…
Role of Sortilin in Models of Autoimmune Neuroinflammation
2015
Abstract The proneurotrophin receptor sortilin is a protein with dual functions, being involved in intracellular protein transport, as well as cellular signal transduction. The relevance of the receptor for various neuronal disorders, such as dementia, seizures, and brain injury, is well established. In contrast, little is known about the role of sortilin in immune cells and inflammatory diseases. The aim of our study was to elucidate the distribution of sortilin in different immune cell types in mice and humans and to analyze its function in autoimmune CNS inflammation. Sortilin was expressed most profoundly in murine and human macrophages and dendritic cells and to a much lesser extent in…
Cytosolic RIG-I–like helicases act as negative regulators of sterile inflammation in the CNS
2011
The action of cytosolic RIG-I-like helicases (RLHs) in the CNS during autoimmunity is largely unknown. Using a mouse model of multiple sclerosis, we found that mice lacking the RLH adaptor IPS-1 developed exacerbated disease that was accompanied by markedly higher inflammation, increased axonal damage and elevated demyelination with increased encephalitogenic immune responses. Furthermore, activation of RLH ligands such as 5'-triphosphate RNA oligonucleotides decreased CNS inflammation and improved clinical signs of disease. RLH stimulation repressed the maintenance and expansion of committed T(H)1 and T(H)17 cells, whereas T-cell differentiation was not altered. Notably, T(H)1 and T(H)17 s…
Immune regulatory neural stem/precursor cells protect from central nervous system autoimmunity by restraining dendritic cell function.
2009
Background: The systemic injection of neural stem/precursor cells (NPCs) provides remarkable amelioration of the clinicopathological features of experimental autoimmune encephalomyelitis (EAE). This is dependent on the capacity of transplanted NPCs to engage concurrent mechanisms of action within specific microenvironments in vivo. Among a wide range of therapeutic actions alternative to cell replacement, neuroprotective and immune modulatory capacities of transplanted NPCs have been described. However, lacking is a detailed understanding of the mechanisms by which NPCs exert their therapeutic plasticity. This study was designed to identify the first candidate that exemplifies and sustains …
T helper cell- and CD40-dependent germline IgM prevents chronic virus-induced demyelinating disease
2012
Generation of antiviral IgM is usually considered as a marker of a short-lived initial antibody response that is replaced by hypermutated and more-efficient IgG. However, once viruses have established a particular niche for their persistence (e.g., within the CNS), the immune system has to specifically mobilize a broad range of antimicrobial effectors to contain the pathogen in the long term. Infection of the CNS with the mouse hepatitis virus (MHV) provides a unique model situation in which the extent of inflammatory CNS disease is determined by the balance between antiviral immune control, viral replication, and immune-mediated damage. We show here that whereas antibody- or B cell-defici…
Innate and adaptive immune responses in the CNS.
2015
Almost every disorder of the CNS is said to have an inflammatory component, but the precise nature of inflammation in the CNS is often imprecisely defined, and the role of CNS-resident cells is uncertain compared with that of cells that invade the tissue from the systemic immune compartment. To understand inflammation in the CNS, the term must be better defined, and the response of tissue to disturbances in homoeostasis (eg, neurodegenerative processes) should be distinguished from disorders in which aberrant immune responses lead to CNS dysfunction and tissue destruction (eg, autoimmunity). Whether the inflammatory tissue response to injury is reparative or degenerative seems to be depende…
Host microbiota constantly control maturation and function of microglia in the CNS.
2015
As the tissue macrophages of the CNS, microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. We observed substantial contributions of the host microbiota to microglia homeostasis, as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype, leading to impaired innate immune responses. Temporal eradication of host microbiota severely changed microglia properties. Limited microbiota complexity also resulted in defective microglia. In contrast, recolonization with a complex microbiota partially restored microglia features. We determ…