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1.
Sci Adv ; 9(47): eadi6855, 2023 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-38000031

RESUMO

Neuroinflammation causes neuronal injury in multiple sclerosis (MS) and other neurological diseases. MicroRNAs (miRNAs) are important modulators of neuronal stress responses, but knowledge about their contribution to neuronal protection or damage during inflammation is limited. Here, we constructed a regulatory miRNA-mRNA network of inflamed motor neurons by leveraging cell type-specific miRNA and mRNA sequencing of mice undergoing experimental autoimmune encephalomyelitis (EAE). We found robust induction of miR-92a in inflamed spinal cord neurons and identified cytoplasmic polyadenylation element-binding protein 3 (Cpeb3) as a key target of miR-92a-mediated posttranscriptional silencing. We detected CPEB3 repression in inflamed neurons in murine EAE and human MS. Moreover, both miR-92a delivery and Cpeb3 deletion protected neuronal cultures against excitotoxicity. Supporting a detrimental effect of Cpeb3 in vivo, neuron-specific deletion in conditional Cpeb3 knockout animals led to reduced inflammation-induced clinical disability in EAE. Together, we identified a neuroprotective miR-92a-Cpeb3 axis in neuroinflammation that might serve as potential treatment target to limit inflammation-induced neuronal damage.


Assuntos
Encefalomielite Autoimune Experimental , MicroRNAs , Esclerose Múltipla , Humanos , Camundongos , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Doenças Neuroinflamatórias , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/metabolismo , Inflamação/genética , Inflamação/metabolismo , Neurônios/metabolismo , RNA Mensageiro/metabolismo , Camundongos Endogâmicos C57BL , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
2.
Elife ; 102021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33565962

RESUMO

While transcripts of neuronal mitochondrial genes are strongly suppressed in central nervous system inflammation, it is unknown whether this results in mitochondrial dysfunction and whether an increase of mitochondrial function can rescue neurodegeneration. Here, we show that predominantly genes of the electron transport chain are suppressed in inflamed mouse neurons, resulting in impaired mitochondrial complex IV activity. This was associated with post-translational inactivation of the transcriptional co-regulator proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). In mice, neuronal overexpression of Ppargc1a, which encodes for PGC-1α, led to increased numbers of mitochondria, complex IV activity, and maximum respiratory capacity. Moreover, Ppargc1a-overexpressing neurons showed a higher mitochondrial membrane potential that related to an improved calcium buffering capacity. Accordingly, neuronal deletion of Ppargc1a aggravated neurodegeneration during experimental autoimmune encephalomyelitis, while neuronal overexpression of Ppargc1a ameliorated it. Our study provides systemic insights into mitochondrial dysfunction in neurons during inflammation and commends elevation of mitochondrial activity as a promising neuroprotective strategy.


Multiple sclerosis is a life-long neurological condition that typically begins when people are in their twenties or thirties. Symptoms vary between individuals, and within a single individual over time, but can include difficulties with vision, balance, movement and thinking. These occur because the immune system of people with multiple sclerosis attacks the brain and spinal cord. This immune assault damages neurons and can eventually cause them to die. But exactly how this happens is unclear, and there are no drugs available that can prevent it. One idea is that the immune attack in multiple sclerosis damages neurons by disrupting structures inside them called mitochondria. These cellular 'organs', or organelles, produce the energy that all cells need to function correctly. If the mitochondria fail to generate enough energy, the cells can die. And because neurons are very active cells with high energy demands, they are particularly vulnerable to the effects of mitochondrial damage. By studying a mouse version of multiple sclerosis, Rosenkranz et al. now show that mitochondria in the neurons of affected animals are less active than those of healthy control mice. This is because the genes inside mitochondria that enable the organelles to produce energy are less active in the multiple sclerosis mice. Most of these genes that determine mitochondrial activity and energy production are under the control of a single master gene called PGC-1alpha. Rosenkranz et al. showed that boosting the activity of this gene ­ by introducing extra copies of it into neurons ­ increases mitochondrial activity in mice. It also makes the animals more resistant to the effects of multiple sclerosis. Boosting the activity of mitochondria in neurons could thus be a worthwhile therapeutic strategy to investigate for multiple sclerosis. Future studies should examine whether drugs that activate PGC-1alpha, for example, could help prevent neuronal death and the resulting symptoms of multiple sclerosis.


Assuntos
Mitocôndrias/metabolismo , Esclerose Múltipla/prevenção & controle , Neurônios/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Masculino , Camundongos
3.
Front Cell Dev Biol ; 8: 849, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32974355

RESUMO

Blood-brain barrier (BBB) dysfunction is critically involved in determining the extent of several central nervous systems (CNS) pathologies and here in particular neuroinflammatory conditions. Inhibiting BBB breakdown could reduce the level of vasogenic edema and the number of immune cells invading the CNS, thereby counteracting neuronal injury. Transient receptor potential (TRP) channels have an important role as environmental sensors and constitute attractive therapeutic targets that are involved in calcium homeostasis during pathologies of the CNS. Transient receptor potential vanilloid 4 (TRPV4) is a calcium permeable, non-selective cation channel highly expressed in endothelial cells. As it is involved in the regulation of the blood brain barrier permeability and consequently cerebral edema formation, we anticipated a regulatory role of TRPV4 in CNS inflammation and subsequent neuronal damage. Here, we detected an increase in transendothelial resistance in mouse brain microvascular endothelial cells (MbMECs) after treatment with a selective TRPV4 inhibitor. However, this effect was abolished after the addition of IFNγ and TNFα indicating that inflammatory conditions override TRPV4-mediated permeability. Accordingly, we did not observe a protection of Trpv4-deficient mice when compared to wildtype controls in a preclinical model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), and no differences in infarct sizes following transient middle cerebral artery occlusion (tMCAO), the experimental stroke model, which leads to an acute postischemic inflammatory response. Furthermore, Evans Blue injections did not show differences in alterations of the blood brain barrier (BBB) permeability between genotypes in both animal models. Together, TRPV4 does not regulate brain microvascular endothelial permeability under inflammation.

4.
Nat Neurosci ; 22(6): 887-896, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31011226

RESUMO

Multiple sclerosis (MS) is characterized by inflammatory insults that drive neuroaxonal injury. However, knowledge about neuron-intrinsic responses to inflammation is limited. By leveraging neuron-specific messenger RNA profiling, we found that neuroinflammation leads to induction and toxic accumulation of the synaptic protein bassoon (Bsn) in the neuronal somata of mice and patients with MS. Neuronal overexpression of Bsn in flies resulted in reduction of lifespan, while genetic disruption of Bsn protected mice from inflammation-induced neuroaxonal injury. Notably, pharmacological proteasome activation boosted the clearance of accumulated Bsn and enhanced neuronal survival. Our study demonstrates that neuroinflammation initiates toxic protein accumulation in neuronal somata and advocates proteasome activation as a potential remedy.


Assuntos
Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Proteínas do Tecido Nervoso/metabolismo , Animais , Drosophila , Humanos , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Neurônios/metabolismo , Neurônios/patologia , Medula Espinal/metabolismo , Medula Espinal/patologia
5.
Nat Microbiol ; 3(10): 1161-1174, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30202017

RESUMO

Congenital Zika virus (ZIKV) syndrome may cause fetal microcephaly in ~1% of affected newborns. Here, we investigate whether the majority of clinically inapparent newborns might suffer from long-term health impairments not readily visible at birth. Infection of immunocompetent pregnant mice with high-dose ZIKV caused severe offspring phenotypes, such as fetal death, as expected. By contrast, low-dose (LD) maternal ZIKV infection resulted in reduced fetal birth weight but no other obvious phenotypes. Male offspring born to LD ZIKV-infected mothers had increased testosterone (TST) levels and were less likely to survive in utero infection compared to their female littermates. Males also presented an increased number of immature neurons in apical and basal hippocampal dendrites, while female offspring had immature neurons in basal dendrites only. Moreover, male offspring with high but not very high (storm) TST levels were more likely to suffer from learning and memory impairments compared to females. Future studies are required to understand the impact of TST on neuropathological and neurocognitive impairments in later life. In summary, increased sex-specific vigilance is required in countries with high ZIKV prevalence, where impaired neurodevelopment may be camouflaged by a healthy appearance at birth.


Assuntos
Transtornos Neurocognitivos/etiologia , Complicações Infecciosas na Gravidez , Infecção por Zika virus/complicações , Zika virus , Animais , Animais Recém-Nascidos , Encéfalo/patologia , Modelos Animais de Doenças , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas , Deficiências da Aprendizagem/etiologia , Masculino , Transtornos Neurocognitivos/patologia , Transtornos Neurocognitivos/fisiopatologia , Insuficiência Placentária , Gravidez , Fatores Sexuais , Testosterona/sangue , Infecção por Zika virus/transmissão
6.
JCI Insight ; 1(19): e89810, 2016 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-27882351

RESUMO

Counteracting the progressive neurological disability caused by neuronal and axonal loss is the major unmet clinical need in multiple sclerosis therapy. However, the mechanisms underlying irreversible neuroaxonal degeneration in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) are not well understood. A long-standing hypothesis holds that the distribution of voltage-gated sodium channels along demyelinated axons contributes to neurodegeneration by increasing neuroaxonal sodium influx and energy demand during CNS inflammation. Here, we tested this hypothesis in vivo by inserting a human gain-of-function mutation in the mouse NaV1.2-encoding gene Scn2a that is known to increase NaV1.2-mediated persistent sodium currents. In mutant mice, CNS inflammation during EAE leads to elevated neuroaxonal degeneration and increased disability and lethality compared with wild-type littermate controls. Importantly, immune cell infiltrates were not different between mutant EAE mice and wild-type EAE mice. Thus, this study shows that increased neuronal NaV1.2 activity exacerbates inflammation-induced neurodegeneration irrespective of immune cell alterations and identifies NaV1.2 as a promising neuroprotective drug target in multiple sclerosis.


Assuntos
Axônios/patologia , Encefalomielite Autoimune Experimental/patologia , Mutação com Ganho de Função , Canal de Sódio Disparado por Voltagem NAV1.2/genética , Degeneração Neural/patologia , Animais , Encefalomielite Autoimune Experimental/genética , Técnicas de Introdução de Genes , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla
7.
Sci Immunol ; 1(3): eaaf8665, 2016 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-28783680

RESUMO

Skin-migratory dendritic cells (migDCs) are pivotal antigen-presenting cells that continuously transport antigens to draining lymph nodes and regulate immune responses. However, identification of migDCs is complicated by the lack of distinguishing markers, and it remains unclear which molecules determine their migratory capacity during inflammation. We show that, in the skin, the neuronal plasticity molecule activity-regulated cytoskeleton-associated protein/activity-regulated gene 3.1 (Arc/Arg3.1) was strictly confined to migDCs. Mechanistically, Arc/Arg3.1 was required for accelerated DC migration during inflammation because it regulated actin dynamics through nonmuscle myosin II. Accordingly, Arc/Arg3.1-dependent DC migration was critical for mounting T cell responses in experimental autoimmune encephalomyelitis and allergic contact dermatitis. Thus, Arc/Arg3.1 was restricted to migDCs in the skin and drove fast DC migration by exclusively coordinating cytoskeletal changes in response to inflammatory challenges. These findings commend Arc/Arg3.1 as a universal switch in migDCs that may be exploited to selectively modify immune responses.

8.
Stroke ; 45(11): 3395-402, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25236871

RESUMO

BACKGROUND AND PURPOSE: Brain injury during stroke results in oxidative stress and the release of factors that include extracellular Ca(2+), hydrogen peroxide, adenosine diphosphate ribose, and nicotinic acid adenine dinucleotide phosphate. These alterations of the extracellular milieu change the activity of transient receptor potential melastatin subfamily member 2 (TRPM2), a nonselective cation channel expressed in the central nervous system and the immune system. Our goal was to evaluate the contribution of TRPM2 to the tissue damage after stroke. METHODS: In accordance with current quality guidelines, we independently characterized Trpm2 in a murine ischemic stroke model in 2 different laboratories. RESULTS: Gene deficiency of Trpm2 resulted in significantly improved neurological outcome and decreased infarct size. Besides an already known moderate neuroprotective effect of Trpm2 deficiency in vitro, ischemic brain invasion by neutrophils and macrophages was particularly reduced in Trpm2-deficient mice. Bone marrow chimeric mice revealed that Trpm2 deficiency in the peripheral immune system is responsible for the protective phenotype. Furthermore, experiments with mixed bone marrow chimeras demonstrated that Trpm2 is essential for the migration of neutrophils and, to a lesser extent, also of macrophages into ischemic hemispheres. Notably, the pharmacological TRPM2 inhibitor, N-(p-amylcinnamoyl)anthranilic acid, was equally protective in the stroke model. CONCLUSIONS: Although a neuroprotective effect of TRPM2 in vitro is well known, we can show for the first time that the detrimental role of TRPM2 in stroke primarily depends on its role in activating peripheral immune cells. Targeting TRPM2 systemically represents a promising therapeutic approach for ischemic stroke.


Assuntos
Isquemia Encefálica/imunologia , Movimento Celular/imunologia , Imunidade Celular/imunologia , Acidente Vascular Cerebral/imunologia , Canais de Cátion TRPM/fisiologia , Animais , Isquemia Encefálica/patologia , Células Cultivadas , Hipocampo/imunologia , Hipocampo/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Técnicas de Cultura de Órgãos , Distribuição Aleatória , Acidente Vascular Cerebral/patologia
9.
Nat Rev Neurol ; 10(4): 225-38, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24638138

RESUMO

Multiple sclerosis (MS) is the most frequent chronic inflammatory disease of the CNS, and imposes major burdens on young lives. Great progress has been made in understanding and moderating the acute inflammatory components of MS, but the pathophysiological mechanisms of the concomitant neurodegeneration--which causes irreversible disability--are still not understood. Chronic inflammatory processes that continuously disturb neuroaxonal homeostasis drive neurodegeneration, so the clinical outcome probably depends on the balance of stressor load (inflammation) and any remaining capacity for neuronal self-protection. Hence, suitable drugs that promote the latter state are sorely needed. With the aim of identifying potential novel therapeutic targets in MS, we review research on the pathological mechanisms of neuroaxonal dysfunction and injury, such as altered ion channel activity, and the endogenous neuroprotective pathways that counteract oxidative stress and mitochondrial dysfunction. We focus on mechanisms inherent to neurons and their axons, which are separable from those acting on inflammatory responses and might, therefore, represent bona fide neuroprotective drug targets with the capability to halt MS progression.


Assuntos
Axônios/patologia , Esclerose Múltipla/patologia , Degeneração Neural/patologia , Animais , Apoptose/fisiologia , Biomarcadores , Humanos , Esclerose Múltipla/genética , Degeneração Neural/genética , Transdução de Sinais/fisiologia , Degeneração Walleriana/patologia , Degeneração Walleriana/fisiopatologia
10.
Exp Neurol ; 262 Pt A: 28-36, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24656770

RESUMO

Multiple sclerosis (MS), the most frequent inflammatory disease of the central nervous system (CNS), affects about two and a half million individuals worldwide and causes major burdens to the patients, which develop the disease usually at the age of 20 to 40. MS is likely referable to a breakdown of immune cell tolerance to CNS self-antigens resulting in focal immune cell infiltration, activation of microglia and astrocytes, demyelination and axonal and neuronal loss. Here we discuss how altered expression patterns and dysregulated functions of ion channels contribute on a molecular level to nearly all pathophysiological steps of the disease. In particular the detrimental redistribution of ion channels along axons, as well as neuronal excitotoxicity with regard to imbalanced glutamate homeostasis during chronic CNS inflammation will be discussed in detail. Together, we describe which ion channels in the immune and nervous system commend as attractive future drugable targets in MS treatment.


Assuntos
Sistema Nervoso Central/patologia , Canalopatias/complicações , Esclerose Múltipla/etiologia , Animais , Sistema Nervoso Central/imunologia , Progressão da Doença , Humanos
11.
Neurobiol Dis ; 59: 177-82, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23932916

RESUMO

OBJECTIVE: We aimed at validating a plasma biomarker for neuronal damage that can be used in acute and chronic models of neurological diseases. METHODS: We investigated two different models, middle cerebral artery occlusion followed by reperfusion and MOG35-55-induced experimental autoimmune encephalomyelitis (EAE). In stroke experiments we measured infarct sizes by magnetic resonance imaging and vital stainings and correlated them with plasma levels of neuron specific enolase (NSE) at different time points after reperfusion. Equally, in EAE experiments, we correlated NSE levels with neurological scores and histopathological damage of axons at different time points. We detected plasma NSE levels by ELISA. RESULTS: Plasma NSE levels correlated significantly with stroke size, EAE score and histopathological damage in EAE. Investigations into the dynamics of neuronal loss over time correlated well with the dynamics of NSE levels. NSE even predicted the onset of EAE, before clinical signs were recordable. CONCLUSIONS: Plasma NSE is a valid and simple experimental biomarker that allows quantifying the degree of neuronal injury in a non-invasive approach.


Assuntos
Infarto da Artéria Cerebral Média/sangue , Infarto da Artéria Cerebral Média/patologia , Esclerose Múltipla/sangue , Esclerose Múltipla/patologia , Neurônios/patologia , Fosfopiruvato Hidratase/sangue , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Encéfalo/citologia , Infarto Encefálico/etiologia , Infarto Encefálico/patologia , Células Cultivadas , Modelos Animais de Doenças , Embrião de Mamíferos , Ácido Glutâmico/toxicidade , L-Lactato Desidrogenase/metabolismo , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo , Esclerose Múltipla/induzido quimicamente , Glicoproteína Mielina-Oligodendrócito/toxicidade , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fragmentos de Peptídeos/toxicidade , Fatores de Tempo
12.
Psychiatry Res ; 208(2): 194-6, 2013 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-23246244

RESUMO

Autoimmune encephalitis associated with IgG antibodies to the N-methyl-d-aspartic acid receptor subunit NR1 (NMDAR) presents with neurological symptoms, such as seizures, and especially psychiatric symptoms, such as hallucinations, psychosis, agitation and anxiety. To date, however, the pathological relevance of IgM NMDAR antibodies remains elusive. Here, we describe clinical, neuroradiological and neurobiological findings of a 28-year-old male presenting with IgM NMDAR antibodies coincident with autoimmune encephalitis characterized by symptoms of bipolar disorder. After repeated steroid treatment, cognitive and psychiatric abnormalities improved and no NMDAR antibody was detectable. Using primary neuronal cultures, we demonstrate that patient's serum containing IgM NMDAR antibodies reduced the detection of NMDAR on neuronal cells and decreased cell survival. Although NMDAR encephalitis with IgG antibodies is increasingly recognized and diagnosed, atypical presentations with NMDAR antibodies with immunoglobulin subclasses other than IgG pose a diagnostic and therapeutic challenge. Further clinical and neurobiological studies are needed to study the pathophysiological relevance of IgM NMDAR antibodies.


Assuntos
Transtorno Bipolar/diagnóstico , Encefalopatias/imunologia , Doença de Hashimoto/imunologia , Imunoglobulina M/imunologia , Imunoglobulina M/farmacologia , Receptores de N-Metil-D-Aspartato/imunologia , Adulto , Encefalopatias/fisiopatologia , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Encefalite , Doença de Hashimoto/fisiopatologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Humanos , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/fisiologia , Cultura Primária de Células , Receptores de N-Metil-D-Aspartato/metabolismo
13.
Nat Med ; 18(12): 1805-11, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23160238

RESUMO

In multiple sclerosis, an inflammatory disease of the central nervous system (CNS), axonal and neuronal loss are major causes for irreversible neurological disability. However, which molecules contribute to axonal and neuronal injury under inflammatory conditions remains largely unknown. Here we show that the transient receptor potential melastatin 4 (TRPM4) cation channel is crucial in this process. TRPM4 is expressed in mouse and human neuronal somata, but it is also expressed in axons in inflammatory CNS lesions in experimental autoimmune encephalomyelitis (EAE) in mice and in human multiple sclerosis tissue. Deficiency or pharmacological inhibition of TRPM4 using the antidiabetic drug glibenclamide resulted in reduced axonal and neuronal degeneration and attenuated clinical disease scores in EAE, but this occurred without altering EAE-relevant immune function. Furthermore, Trpm4(-/-) mouse neurons were protected against inflammatory effector mechanisms such as excitotoxic stress and energy deficiency in vitro. Electrophysiological recordings revealed TRPM4-dependent neuronal ion influx and oncotic cell swelling upon excitotoxic stimulation. Therefore, interference with TRPM4 could translate into a new neuroprotective treatment strategy.


Assuntos
Axônios/metabolismo , Encefalomielite Autoimune Experimental/metabolismo , Esclerose Múltipla/metabolismo , Degeneração Neural/metabolismo , Canais de Cátion TRPM/metabolismo , Análise de Variância , Animais , Axônios/efeitos dos fármacos , Western Blotting , Proliferação de Células/efeitos dos fármacos , Primers do DNA/genética , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Glibureto/farmacologia , Humanos , Imuno-Histoquímica , Hibridização In Situ , Camundongos , Camundongos Knockout , Técnicas de Patch-Clamp , Reação em Cadeia da Polimerase em Tempo Real , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Canais de Cátion TRPM/antagonistas & inibidores , Canais de Cátion TRPM/genética
14.
Exp Dermatol ; 19(8): e80-8, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19849712

RESUMO

Cathepsin S (CATS) is a cysteine protease, well known for its role in MHC class II-mediated antigen presentation and extracellular matrix degradation. Disturbance of the expression or metabolism of this protease is a concomitant feature of several diseases. Given this importance we studied the localization and regulation of CATS expression in normal and pathological human/mouse skin. In normal human skin CATS-immunostaining is mainly present in the dermis and is localized in macrophages, Langerhans, T- and endothelial cells, but absent in keratinocytes. In all analyzed pathological skin biopsies, i.e. atopic dermatitis, actinic keratosis and psoriasis, CATS staining is strongly increased in the dermis. But only in psoriasis, CATS-immunostaining is also detectable in keratinocytes. We show that cocultivation with T-cells as well as treatment with cytokines can trigger expression and secretion of CATS, which is involved in MHC II processing in keratinocytes. Our data provide first evidence that CATS expression (i) is selectively induced in psoriatic keratinocytes, (ii) is triggered by T-cells and (iii) might be involved in keratinocytic MHC class II expression, the processing of the MHC class II-associated invariant chain and remodeling of the extracellular matrix. This paper expands our knowledge on the important role of keratinocytes in dermatological disease.


Assuntos
Catepsinas/metabolismo , Queratinócitos/metabolismo , Psoríase/metabolismo , Regulação para Cima/fisiologia , Animais , Biópsia , Comunicação Celular , Linhagem Celular , Técnicas de Cocultura , Citocinas/farmacologia , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Modelos Animais de Doenças , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/patologia , Complexo Principal de Histocompatibilidade , Camundongos , Oxazolona/efeitos adversos , Psoríase/patologia , Linfócitos T/patologia
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