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LPS expands MDSCs by inhibiting apoptosis through the regulation of the GATA2/let-7e axis

ABSTRACT: Myeloid-derived suppressor cells (MDSCs) represent a group of immature myeloid cells composed of myeloid progenitor cells and immature myeloid cells that can negatively regulate immune responses by inhibiting T cell function. Our lab and other groups have shown that injection of a lethal or sublethal dose of LPS into mice can result in the expansion of MDSCs in the bone marrow, spleen and blood. Until now, the molecular mechanisms responsible for this expansion were poorly studied. Specifically, the role of the individual microRNAs (miRNAs) involved remained largely unknown. We performed microarray analysis to compare the miRNA expression profiles of Gr-1+CD11b+ cells sorted from the bone marrow of LPS-injected and PBS-injected mice. We identified let-7e, which was highly upregulated in the LPS-treated group, as a potent regulator of LPS-induced MDSC expansion. Furthermore, let-7e overexpression in bone marrow chimeric mice leads to a noticeable increase in the population of Gr-1+CD11b+ cells, which results from reduced cellular apoptosis. Further studies showed that let-7e can directly target caspase-3 to inhibit cell apoptosis, and upregulation of let-7e in LPS-stimulated MDSCs could be due to the relieved repression of let-7e transcription exerted by downregulated GATA2. Our findings suggest that LPS expands MDSCs by inhibiting apoptosis through the regulation of the GATA2/let-7e axis.

ORGANISM(S): Mus musculus Rattus norvegicus Homo sapiens

PROVIDER: GSE118398 | GEO | 2018/08/11

REPOSITORIES: GEO

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LPS expands MDSCs by inhibiting apoptosis through the regulation of the GATA2/let-7e axis

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