PXD010804

PXD010804 is an original dataset announced via ProteomeXchange.

Title	Immunoregulatory Effects of Myeloid-Derived Suppressor Cell Exosomes in Mouse Model of Autoimmune Alopecia Areata
Description	We have demonstrated therapeutic efficacy of MDSC in mouse Alopecia Areata (AA). In the same AA model, we now asked whether MDSC exosomes (MDSC-Exo) can replace MDSC. MDSC-Exo from bone marrow cells (BMC) cultures of healthy donors could substantially facilitate treatment. With knowledge on MDSC-Exo being limited, their suitability needs to be verified in advance. Protein marker profiles suggest comparability of BMC- to ex vivo collected inflammatory MDSC/MDSC-Exo in mice with a chronic contact dermatitis, which is a therapeutic option in AA. Proteome analyses substantiated a large overlap of function-relevant molecules in MDSC and MDSC-Exo. Furthermore, MDSC-Exo are taken up by T cells, macrophages, NK, and most avidly by Treg and MDSC-Exo uptake exceeds binding of MDSC themselves. In AA mice, MDSC-Exo preferentially target skin-draining lymph nodes and cells in the vicinity of remnant hair follicles. MDSC-Exo uptake is accompanied by a strong increase in Treg, reduced T helper proliferation, mitigated cytotoxic activity, and a slight increase in lymphocyte apoptosis. Repeated MDSC-Exo application in florid AA prevented progression and sufficed for partial hair regrowth. Deep sequencing of lymphocyte mRNA from these mice revealed a significant increase in immunoregulatory mRNA, including FoxP3 and arginase 1. Downregulated mRNA was preferentially engaged in prohibiting T cell hyperreactivity. Taken together, proteome analysis provided important insights into potential MDSC-Exo activities, these Exo preferentially homing into AA-affected organs. Most importantly, changes in leukocyte mRNA seen after treatment of AA mice with MDSC-Exo sustainably supports the strong impact on the adaptive and the non-adaptive immune system, with Treg expansion being a dominant feature. Thus, MDSC-Exo could potentially serve as therapeutic agents in treating AA and other autoimmune diseases. These shotgun data represent GeLC-MS/MS analyses of murine MDSC and CDMS+ cells and of the exosomes from both cell types. Three pulldown RPLC-MS/MS experiments are also included. Cysteines were carbamidomethylated via iodoacetamide. Tandem mass spectrometry took place in an LTQ Orbitrap XL, with scans acquired in the linear ion trap.
HostingRepository	MassIVE
AnnounceDate	2018-08-17
AnnouncementXML	Submission_2018-08-17_01:03:03.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	David L. Tabb
SpeciesList	scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationList	Carbamidomethyl; Oxidation
Instrument	LTQ Orbitrap XL

Revision	Datetime	Status	ChangeLog Entry
0	2018-08-16 23:32:38	ID requested
⏵ 1	2018-08-17 01:03:04	announced

Z, ö, ller M, Zhao K, Kutlu N, Bauer N, Provaznik J, Hackert T, Schn, ö, lzer M, Immunoregulatory Effects of Myeloid-Derived Suppressor Cell Exosomes in Mouse Model of Autoimmune Alopecia Areata. Front Immunol, 9():1279(2018) [pubmed]

submitter keyword: myeloid-derived suppressor cells, exosomes

Margot Zoeller
contact affiliation	University Hospital of Heidelberg
contact email	margot.zoeller@gmx.net
lab head
David L. Tabb
contact affiliation	Vanderbilt University Medical Center
contact email	david.l.tabb@vanderbilt.edu
dataset submitter

MassIVE dataset URI

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://massive.ucsd.edu/MSV000082825