Contributions
Abstract: 195
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Demyelination is a hallmark of Multiple Sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) pathology and appears in both, the relapsing-remitting and chronic-progressive phase of the disease.
The degree of demyelination correlates with the severity of clinical signs in MS and EAE, conversely remyelination links to functional recovery, but fails during progressive MS and EAE. We have recently shown that microglia have the potential to drive endogenous repair, including oligodendrogenesis by suventricular zone (SVZ) neural stem cells (NSCs). However, microglia"s niche supporting functions seem only active during acute neuroinflammation but fail during the chronic progressive disease phase.
Here, we identified Chi3l3 (Ym1), an endogenous C-type lectin and secreted marker of alternative microglia/macrophages, as a pivotal regulator of oligodendrocyte regeneration. Chi3l3 drives differentiation of neural stem cells towards the oligodendroglial lineage by inducing a prooligodendrogenic transcription factor signature in a mitogen-activated protein kinase (MAPK) signalling dependent manner. In vivo, Endogenous Chi3l3 was highly expressed during the acute phase of EAE and its targeted deletion resulted in severely impaired remission during EAE.
Thus, Chi3l3 plays an important role in driving oligodendrocyte regeneration and is essential in EAE recovery, with critical therapeutic implications for MS.
Disclosure:
Sarah Starossom: nothing to disclose
Marta Olah: nothing to disclose
Li Cao: nothing to disclose
Ada Yeste: nothing to disclose
Francisco J. Quintana: nothing to disclose
Jaime Imitola: nothing to disclose
Friedemann Paul: received research upport and speaker honorary from various pharamceutical companies
Carmen Infante-Duarte: nothing to disclose
Samia J Khoury: nothing to disclose
Abstract: 195
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Demyelination is a hallmark of Multiple Sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) pathology and appears in both, the relapsing-remitting and chronic-progressive phase of the disease.
The degree of demyelination correlates with the severity of clinical signs in MS and EAE, conversely remyelination links to functional recovery, but fails during progressive MS and EAE. We have recently shown that microglia have the potential to drive endogenous repair, including oligodendrogenesis by suventricular zone (SVZ) neural stem cells (NSCs). However, microglia"s niche supporting functions seem only active during acute neuroinflammation but fail during the chronic progressive disease phase.
Here, we identified Chi3l3 (Ym1), an endogenous C-type lectin and secreted marker of alternative microglia/macrophages, as a pivotal regulator of oligodendrocyte regeneration. Chi3l3 drives differentiation of neural stem cells towards the oligodendroglial lineage by inducing a prooligodendrogenic transcription factor signature in a mitogen-activated protein kinase (MAPK) signalling dependent manner. In vivo, Endogenous Chi3l3 was highly expressed during the acute phase of EAE and its targeted deletion resulted in severely impaired remission during EAE.
Thus, Chi3l3 plays an important role in driving oligodendrocyte regeneration and is essential in EAE recovery, with critical therapeutic implications for MS.
Disclosure:
Sarah Starossom: nothing to disclose
Marta Olah: nothing to disclose
Li Cao: nothing to disclose
Ada Yeste: nothing to disclose
Francisco J. Quintana: nothing to disclose
Jaime Imitola: nothing to disclose
Friedemann Paul: received research upport and speaker honorary from various pharamceutical companies
Carmen Infante-Duarte: nothing to disclose
Samia J Khoury: nothing to disclose