Contributions
Abstract: EP1505
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 18 Neurobiology
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) in which inflammation plays a key pathological role. The anti-inflammatory enzyme A20 is considered a central gatekeeper in inflammation and immunity through the inhibition of NF-kB. Polymorphisms in A20 genomic-region has been recently associated to MS and we observed an A20 down-regulation in peripheral blood cells of MS patients, mainly due to monocytes, correlated to a worst clinical course.
Recent evidences showed that systemic inflammation induces increasing cell infiltration within the brain parenchyma, triggering resident microglial ad astrocytic activation. Considering the critical role of A20 in systemic inflammation regulation, a function of A20 in the CNS was hypothesized. Supporting this, the presence of A20 transcript and proteins belonging to A20-complex were newly demonstrated in control human brain. Moreover, A20 deletion in neuroectodermal cells worse the clinical course of the MS murine model. From this picture, clearly emerges a double role of A20 in central nervous and immune system.
Here we aimed to unveil the contribution of A20 to the CNS MS pathology, studying for the first time A20 expression in human post-mortem MS brain tissues.
We demonstrated that A20 is present in control human brain tissues in both white matter, mainly in parenchymal astrocytes and in grey matter, in neuronal cells. In MS brain, we observe a massive A20 expression in the lesions in both perivascular infiltrates and ramified cells. In particular, in active and pre-active lesions, A20 is expressed in the active core, whereas in chronic active lesions, A20 is mainly expressed on the active-margin. Preliminary double immunofluorescence staining unveiled that A20 is expressed in both AL and CAL by infiltrating macrophages and by resident activated astrocytes and a subpopulation of microglial cells. Coherently, chronic activation of NF-kB pathway in infiltrating and resident CNS seems an hallmark of the neurodegenerative process occurring in MS patients. In this view, the massive A20 activation in the active plaques could represent a defensive mechanism contributing to the inflammation resolution and the regeneration processes.
Disclosure: The study is supported by the Italian Multiple Sclerosis Foundation (FISM) and by the Italian Ministry of Health.
Perga: has nothing to disclose
Montarolo: has nothing to disclose
Martire: has nothing to disclose
Bonaldo: has nothing to disclose
Bono: has nothing to disclose
Panzica: has nothing to discolose
Bertolotto: has nothing to disclose
Abstract: EP1505
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 18 Neurobiology
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) in which inflammation plays a key pathological role. The anti-inflammatory enzyme A20 is considered a central gatekeeper in inflammation and immunity through the inhibition of NF-kB. Polymorphisms in A20 genomic-region has been recently associated to MS and we observed an A20 down-regulation in peripheral blood cells of MS patients, mainly due to monocytes, correlated to a worst clinical course.
Recent evidences showed that systemic inflammation induces increasing cell infiltration within the brain parenchyma, triggering resident microglial ad astrocytic activation. Considering the critical role of A20 in systemic inflammation regulation, a function of A20 in the CNS was hypothesized. Supporting this, the presence of A20 transcript and proteins belonging to A20-complex were newly demonstrated in control human brain. Moreover, A20 deletion in neuroectodermal cells worse the clinical course of the MS murine model. From this picture, clearly emerges a double role of A20 in central nervous and immune system.
Here we aimed to unveil the contribution of A20 to the CNS MS pathology, studying for the first time A20 expression in human post-mortem MS brain tissues.
We demonstrated that A20 is present in control human brain tissues in both white matter, mainly in parenchymal astrocytes and in grey matter, in neuronal cells. In MS brain, we observe a massive A20 expression in the lesions in both perivascular infiltrates and ramified cells. In particular, in active and pre-active lesions, A20 is expressed in the active core, whereas in chronic active lesions, A20 is mainly expressed on the active-margin. Preliminary double immunofluorescence staining unveiled that A20 is expressed in both AL and CAL by infiltrating macrophages and by resident activated astrocytes and a subpopulation of microglial cells. Coherently, chronic activation of NF-kB pathway in infiltrating and resident CNS seems an hallmark of the neurodegenerative process occurring in MS patients. In this view, the massive A20 activation in the active plaques could represent a defensive mechanism contributing to the inflammation resolution and the regeneration processes.
Disclosure: The study is supported by the Italian Multiple Sclerosis Foundation (FISM) and by the Italian Ministry of Health.
Perga: has nothing to disclose
Montarolo: has nothing to disclose
Martire: has nothing to disclose
Bonaldo: has nothing to disclose
Bono: has nothing to disclose
Panzica: has nothing to discolose
Bertolotto: has nothing to disclose