Chi3l3 induces oligodendrocyte regeneration in a model of multiple sclerosis
Author(s): ,
S.C Starossom
Affiliations:
Institute for Medical Immunology, Charite - Universitätsmedizin Berlin, Berlin, Germany;Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
,
M Olah
Affiliations:
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
,
L Cao
Affiliations:
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
,
A Yeste
Affiliations:
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
,
F.J Quintana
Affiliations:
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
,
J Imitola
Affiliations:
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
,
F Paul
Affiliations:
Clinical and Experimental Multiple Sclerosis Research Center, Neurology, Charite - Universitätsmedizin Berlin, Berlin, Germany
,
C Infante-Duarte
Affiliations:
Institute for Medical Immunology, Charite - Universitätsmedizin Berlin, Berlin, Germany
S.J Khoury
Affiliations:
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
ECTRIMS Online Library. Starossom S. 09/16/16; 147041; 195
Sarah C. Starossom
Sarah C. Starossom
Contributions
Abstract

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

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