A5071980321- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- Immune cells in cancer
- Ocular Diseases and Behçet’s Syndrome
- Nuclear Receptors and Signaling
- Systemic Lupus Erythematosus Research
- Mycobacterium research and diagnosis
- Psoriasis: Treatment and Pathogenesis
- Macrophage Migration Inhibitory Factor
- Amyotrophic Lateral Sclerosis Research
- Immunodeficiency and Autoimmune Disorders
- Retinoids in leukemia and cellular processes
- Gut microbiota and health
- interferon and immune responses
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cytomegalovirus and herpesvirus research
- Tryptophan and brain disorders
- Sphingolipid Metabolism and Signaling
- Inflammasome and immune disorders
- Inflammation biomarkers and pathways
- Nerve injury and regeneration
National Center of Neurology and Psychiatry
2012-2024
RIKEN Center for Integrative Medical Sciences
2024
Institute of Science Tokyo
2022
National Neuroscience Institute
2009
University of Bristol
2004-2009
Bristol Eye Hospital
2008
Abstract Development of acute experimental autoimmune encephalomyelitis (EAE) depends on Th17 cells expressing the nuclear factor NR4A2. However, in mice lacking NR4A2 T cells, a late-onset disease is still inducible, despite great reduction inflammation. We here reveal that development this late onset cytotoxic T-cell-like CD4 + T-box transcription Eomesodermin (Eomes). T-cell-specific deletion Eomes gene remarkably ameliorates EAE. Strikingly, similar are increased peripheral blood and...
Multiple sclerosis (MS), a putative autoimmune disease of the central nervous system (CNS), commonly presents as relapsing-remitting MS (RRMS), characterized by recurrent episodes peripheral disabling symptoms resulting from inflammatory CNS damage. Many RRMS patients transition to chronic course with progressive neurological dysfunctions (secondary MS, SPMS), progression rate varying between and over time. SPMS pathogenesis is now linked immune-cell-mediated processes, although mechanisms...
IL-17-producing CD4+ T helper 17 (Th17) cells are pathogenic in a range of human autoimmune diseases and corresponding animal models. We now demonstrate that such infiltrating the target organ during induction experimental encephalomyelitis (EAE) uveoretinitis (EAU) specifically express NR4A2. Further, we reveal critical involvement NR4A2 Th17 cell functions cell-driven diseases. When expression was blocked with siRNA, full differentiation prevented vitro: although expressed master...
EAU is an established preclinical model for assessment of immunotherapeutic efficacy toward translation therapy posterior uveitis. Reliable screening clinical features that correlate with underlying retinal changes and damage has not been possible to date. This study was undertaken describe, validate, topical endoscopic fundus imaging (TEFI) histologic murine experimental autoimmune uveoretinitis (EAU), the intent generating a rapid noninvasive panretinal ocular inflammation.EAU induced in...
Experimental autoimmune uveoretinitis is an disease induced in mice, which involves the infiltration of CD11b(+) macrophages and CD4(+) T cells into normally immune-privileged retina. Damage produced target organ following activation Th1 Th17 by release cytotoxic mediators such as NO activated macrophages. The majority immune infiltrating retina are myeloid cells, but, despite presence these APCs, relatively limited numbers observed during course. These do not proliferate when leukocytes...
Eomesodermin‐expressing (Eomes + ) T‐helper (Th) cells show cytotoxic characteristics in secondary progressive multiple sclerosis. We found that Eomes Th cell frequency was increased the peripheral blood of amyotrophic lateral sclerosis and Alzheimer's disease patients. Furthermore, granzyme B production by from such patients high compared with controls. A observed initial (acutely progressive) stage sclerosis, a positive correlation between cognitive decline Therefore, may be involved...
Significance We have previously demonstrated that induction of pathogenic eomesodermin-positive CD4 + T cells (Eomes helper [Th] cells) is associated with transition from an acute stage to a later experimental autoimmune encephalomyelitis (EAE). In the late phase EAE, B and non-B cell antigen-presenting (APCs) recruited central nervous system strikingly up-regulate prolactin (PRL). The PRL-producing APCs potential promote generation Eomes Th naïve in MHC class II-restricted manner, therapies...
To examine the efficacy of immunomodulatory drug fingolimod (FTY720) as a rescue therapy for noninfectious intraocular inflammation.Experimental autoimmune uveoretinitis, murine correlate human uveitis, was induced in B10.RIII mice. The mice were treated with 2 oral doses daily, either during early ocular infiltration or following clinical onset disease. At subsequent times, retinal infiltrates examined and enumerated using flow cytometry, structural disease assessed scored...
Neurodegeneration is a process involving both cell autonomous and non-cell neuron loss, followed by collapse of neural networks, but its pathogenesis poorly understood. We have previously demonstrated that Eomes-positive helper T (Eomes + Th) cells recognizing LINE-1(L1)-derived prototypic antigen ORF1 mediate neurotoxicity associated with the neurodegenerative pathology experimental autoimmune encephalomyelitis (EAE). Here, we show Eomes Th accumulate in CNS mouse models authentic diseases,...
Summary Macrophages (Mϕ) are professional antigen‐presenting cells, but when they accumulate at sites of inflammation, can inhibit T‐cell proliferation. In experimental autoimmune uveoretinitis, this limits the expansion T cells within target organ. To define requirements for elaboration outcome, we have generated populations Mϕ in vitro that could also regulate responses; stimulating CD4 + activation and cytokine production, simultaneously suppressing When removed from influence such normal...
In addition to disease-associated microglia (DAM), with MHC-II and/or IFN-I signatures may form additional pathogenic subsets that are relevant neurodegeneration. However, the significance of such and remains elusive. We demonstrate here these microglial play intrinsic roles in orchestrating neurotoxic properties Eomes+ Th cells under neurodegeneration-associated phase experimental autoimmune encephalomyelitis (EAE) corresponds progressive multiple sclerosis (MS). Microglia acquire...
Abstract H-2d mice expressing both the influenza virus hemagglutinin (HA) as a transgene-encoded protein on pancreatic islet β cells (InsHA), well Clone 4 TCR specific for dominant H-2Kd-restricted HA epitope, can be protected from development of spontaneous autoimmune diabetes by expression H-2b haplotype. Protection occurs due to deletion KdHA-specific CD8+ T cells. This was unexpected neither presence InsHA transgene nor H-2b, individually, resulted in thymic deletion. Further analyses...
It is acknowledged that T cell interactions with mature dendritic cells (DC) lead to immunity, whereas immature DC tolerance induction. Using a transgenic murine system, we have examined how expressing self-peptides control naive, self-reactive CD8+ responses in vitro and vivo. We shown, for the first time, can also stimulate productive activation of naive self-specific cells, which results extensive proliferation, expression highly activated surface phenotype, differentiation into...
Objectives: Multiple sclerosis (MS) is associated with the activation of CD4 + T helper (Th) cells by self-antigen from central nervous system (CNS) to generate pathogenic self-reactive Th cells.Treat-
InsHA mice express the haemagglutinin (HA) protein from influenza virus A/PR/8 H1N1 (PR8) as a self antigen on pancreatic islet beta cells. We have utilized these to investigate ability of resting B cells expressing Kd induce self-tolerance among naive KdHA-specific clone 4 CD8+ T Adoptive transfer KdHA-peptide-pulsed into 4-->InsHA recipients resulted in activation and proliferation throughout peripheral lymphoid tissues. Significantly, was not associated with acquisition cell effector...