Myeloid‐derived suppressor cell activation by combined LPS and IFN‐γ treatment impairs DC development

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Abstract
Myeloid-derived suppressor cells (MDSC) and DC are major controllers of immune responses against tumors or infections. However, it remains unclear how DC development and MDSC suppressor activity both generated from myeloid precursor cells are regulated. Here, we show that the combined treatment of BM-derived MDSC with LPS plus IFN-γ inhibited the DC development but enhanced MDSC functions, such as NO release and T-cell suppression. This was not observed by the single treatments in vitro. In the spleens of healthy mice, we identified two Gr-1lowCD11bhighLy-6ChighSSClowMo-MDSC and Gr-1highCD11blowPMN-MDSC populations with suppressive potential, whereas Gr-1highCD11bhigh neutrophils and Gr-1lowCD11bhighSSClow eosinophils were not suppressive. Injections of LPS plus IFN-γ expanded these populations within the spleen but not LN leading to the block of the proliferation of CD8+ T cells. At the same time, their capacity to develop into DC was impaired. Together, our data suggest that spleens of healthy mice contain two subsets of MDSC with suppressive potential. A two-signal-program through combined LPS and IFN-γ treatment expands and fully activates MDSC in vitro and in vivo.