Extracellular acidosis drives the differentiation of human monocytes into dendritic-like cells

DANTAS, EZEQUIEL; SABATTÉ JUAN; DÍAZ, FERNANDO ERRA; DUETTE, GABRIEL

Banff

Simposio; HUMAN IMMUNITY- CELL SYMPOSIA; 2017

Differentiation of monocytes into macrophages and inflammatory dendritic cells (DCs) is likely determined by the properties of the inflammatory milieu, however, little is known about the identity of the factors that control the polarization of monocytes toward each of these fates. Extracellular acidosis is a common feature of both inflamed tissues and the tumor environment. We found that low pH (pH 6.5) induced the differentiation of monocytes into dendritic-like cells. Purified monocytes cultured for 7 days at pH 6.5 acquired a DC-like phenotype characterized by the expression of CD1a, CD1c, DC-SIGN, CD80, CD86, HLA-DR, low/undetectable levels of CD14, and a typical DC morphology. Similar findings were observed when peripheral blood mononuclear cells (PBMCs) were stimulated by PHA for 7 days at pH 6.5, as well as when monocytes were cultured with allogeneic T lymphocytes at this pH value. Our results suggest that tissue acidosis might promote the differentiation of monocytes into DCs.