Characterization of monocyte subtypes regarding their phenotype and development in the context of graft-versus-host...

Graft-versus-host disease (GvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). In this study, monocyte subtypes were characterized regarding cytokine expression pattern and development in the context of GvHD. Using inflammatory S100 proteins for monocyte stimulation, it could be demonstrated that intermediate monocytes are the main producers of inflammatory cytokines such as IL-6 and TNFα known to be involved in the development of Th17 cells pointing towards an inflammatory phenotype of this monocyte subtype. Furthermore, novel aspects regarding monocyte subtype development were found. Our data reveal that prednisolone promotes the induction of intermediate monocytes from classical monocytes which correlates with HSP70 expression levels. However, 1α,25-Dihydroxyvitamin D3 treatment results in the abrogation of the prednisolone-mediated induction of this inflammatory monocyte subset and low HSP70 expression levels. Treatment of classical monocytes with pifithrin-μ, a specific HSP70 inhibitor, also leads to an inhibited induction of intermediate monocytes in the presence of prednisolone. These data point towards a predominant role of HSP70 in the development of intermediate monocytes. Thus, HSP70 might be a promising target for GvHD therapy, especially in combination with glucocorticoids, in order to decrease intermediate monocyte subset levels.