PXD014625

PXD014625 is an original dataset announced via ProteomeXchange.

Title	Pro-inflammatory activity following demyelinating injury is required for phagocytic function and oligodendrocyte formation
Description	Remyelination can occur naturally in demyelinating lesions, but often fails in human demyelinating diseases such as multiple sclerosis (MS). The function of the innate immune system is essential for the regenerative response, but how exactly microglia and macrophages clear myelin debris after injury and tailor a specific regenerative response is unclear. Here, we asked whether pro-inflammatory microglial/macrophage activation is required for this process. We established a novel toxin-based spinal cord model of de- and remyelination in zebrafish and showed that pro-inflammatory nuclear factor κB (NF-κB) dependent activation occurs in phagocytes rapidly after myelin injury. We found that the pro-inflammatory response depends on myeloid differentiation primary response 88 (MyD88), the canonical adaptor for inflammatory signaling pathways downstream of toll-like receptors (TLRs). MyD88-deficient mice and zebrafish were impaired not only in the degradation of myelin debris, but also in initiating the generation of new oligodendrocytes for myelin repair. We identified reduced generation of tumor necrosis factor-α (TNF-α) in lesions of MyD88-deficient animals, a pro-inflammatory molecule that was able to induce the generation of new oligodendrocytes. Our study shows that pro-inflammatory phagocytic signaling is an evolutionary conserved mechanism necessary for degrading myelin debris, essential for inflammation resolution, and for initiating the secretion of pro-inflammatory myelin repair molecules.
HostingRepository	PRIDE
AnnounceDate	2020-02-17
AnnouncementXML	Submission_2020-02-24_02:48:19.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stephan Mueller
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-16 00:46:33	ID requested
1	2020-02-17 01:13:08	announced
⏵ 2	2020-02-24 02:48:20	announced	2020-02-24: Updated publication reference for PubMed record(s): 32078678.

Cunha MI, Su M, Cantuti-Castelvetri L, M, ü, ller SA, Schifferer M, Djannatian M, Alexopoulos I, van der Meer F, Winkler A, van Ham TJ, Schmid B, Lichtenthaler SF, Stadelmann C, Simons M, Pro-inflammatory activation following demyelination is required for myelin clearance and oligodendrogenesis. J Exp Med, 217(5):(2020) [pubmed]

curator keyword: Biological

submitter keyword: Microglia, mouse, Myd88, myelin

Stefan Lichtenthaler
contact affiliation	Neuroproteomics DZNE Munich Feodor-Lynen-Str. 17 81377 Munich Germany
contact email	stefan.lichtenthaler@dzne.de
lab head
Stephan Mueller
contact affiliation	DZNE Munich Neuroproteomics
contact email	stephan.mueller@dzne.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD014625

PRIDE project URI

• PRIDE
  1. PXD014625
     1. Label: PRIDE project
     2. Name: Pro-inflammatory activity following demyelinating injury is required for phagocytic function and oligodendrocyte formation