The Ability of Precursory Monocytes (MO) to Differentiate Varies Among Individuals But Is Stable Over Time

单核细胞前体(MO)的分化能力因人而异,但随时间推移保持稳定。

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作者:Krzysztof Laudanski ,Mateusz Zawadka ,Natalia Lapko

Abstract

BACKGROUND The ability to generate dendritic cells (DCs) from precursory monocytes (MOs) was a breakthrough in the field of immunology. However, it is unknown whether the ability of MOs to differentiate into immature DCs (iDCs) differs across subjects or is time dependent. Given that the study of immune system function is gaining recognition in the field of clinical medicine, it is important to know how certain immunologic features vary over time. MATERIAL AND METHODS This study investigates how much individuals' MO-to-iDC differentiation potential changes over time. We estimated this potential by measuring the expression of an iDC marker (CD1a), cytokine secretion (interleukin [IL]-12p70), and the ability of IL-4 and granulocyte macrophage colony-stimulating factor (GM-CSF) differentiation MOs to stimulate T cells. We collected MOs obtained from different subjects (n=17) at least 1 month apart. Furthermore, we investigated several variables (expression for cytokine receptors, timing, and emergence of DC-related transcriptional factor PU.1). RESULTS The ability of MOs to become DCs under the influence of IL-4 and GM-CSF varied greatly between individuals (range of CD1a expression, 20-80%) but was stable over time (change of CD1a expression between sampling, ~5%). A similar pattern emerged when production of IL-12p70 was analyzed. The ability to stimulate T cells was variable and depended on the T-cell source. The ability of MOs to become iDCs was not linked to the surface expression of receptors for IL-4 and GM-CSF but rather to the activation of PU.1 in the precursory MO. It took 5 days for all committed MOs to become iDCs under in vitro influence of IL-4 and GM-CSF. CONCLUSIONS We concluded that the potential of MO to become iDC is an individual feature and depends on activation of PU.1.

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