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Organelle-based therapy for immune mediated disease: mitochondrial transfer elicits Tregs reprogramming

ABSTRACT: Mesenchymal stem cells (MSCs) have fueled ample translation for the treatment of immune mediated diseases. They exert immunoregulatory and tissue restoring effects. MSCmediated transfer of mitochondria (MitoT) had been demonstrated to rescue target organs from tissue damage. While the mechanism remains to be fully resolved, we explored the effect of MitoT on lymphoid cells. Here, we describe dose dependent MitoT from mitochondria-labelled MSCs mainly to T CD4+ rather than to T CD8+ or CD19+ B-cells. Artificial transfer of isolated MSC-derived mitochondria increased the expression of mRNA transcripts involved in T cell activation and T-regulatory cell differentiation including FOXP3, IL2RA, CTLA4 and TGFβ1, leading to an increase of a highly suppressive CD25+FoxP3+ population. In a GVHD mouse model, transplantation of MitoT-induced human T cells led to significant improvement in survival and reduction in tissue damage and organ T CD4+, CD8+ and IFNγ+ expressing cell infiltration. These findings point to a unique CD4+ T cell reprogramming mechanism with pre-clinical proof of concept data that pave the way for the exploration of organelle-based therapies in immune diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE140483 | GEO | 2019/11/16

REPOSITORIES: GEO

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