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Immunoregulatory effects of Myeloid-derived suppressor cell exosomes in autoimmune diseases.

ABSTRACT: Myeloid-derived suppressor cell exosomes have significant immunoregulatory effects in autoimmune disease as exemplified in mouse alopecia areata

PROVIDER: PRJEB25444 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR2380190.fastq.gz	Fastqsanger.gz
	ERR2380191.fastq.gz	Fastqsanger.gz
	ERR2380192.fastq.gz	Fastqsanger.gz
	ERR2380188.fastq.gz	Fastqsanger.gz
	ERR2380189.fastq.gz	Fastqsanger.gz

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Project 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.

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Immunoregulatory effects of Myeloid-derived suppressor cell exosomes in autoimmune diseases.

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