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Generation of Human Monocyte-derived Dendritic Cells from Whole Blood
Published on: December 24, 2016
All-trans retinoic acid inhibits the differentiation, maturation, and function of human monocyte-derived dendritic
Chun-Ji Jin1, Cheol Yi Hong, Masao Takei
1Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Jeonnam, South Korea.
Abstract:
All-trans retinoic acid (ATRA) affects on the function of antigen presenting cells with somewhat controversies. We investigated the effects of ATRA on differentiation, maturation and function of human monocyte-derived dendritic cells (DCs). Low dose (10(-14)M) or high dose (10(-6)M) of ATRA was added either when monocytes were differentiated into immature DCs (imDCs) or mature DCs (mDCs) were induced. Apoptotic cell populations were dramatically increased in imDCs or mDCs with increasing concentration of ATRA. The productions of IL-12p40 and IL-12p70 were significantly suppressed in imDCs or mDCs induced by the addition of ATRA in the dose-dependent manner, whereas IL-10 was increased. DCs cultured with ATRA induced the differentiation of naïve T cells towards a helper T cell type 2 (Th2) response and expansion of CD4(+)CD25(+)Foxp3(+) regulatory T cells. Allostimulatory capacity of DCs was suppressed with increasing concentration of ATRA. These findings suggest that ATRA inhibits the effects on the differentiation, maturation and function of human monocyte-derived DCs in vitro and also enhance the differentiation of naïve T cell toward the Th2 type.
Insights
All-trans retinoic acid (ATRA) significantly suppresses human dendritic cell (DC) differentiation, maturation, and function. ATRA also promotes T cell differentiation towards a Th2 response and regulatory T cells.
Area of Science:
- Immunology
- Cell Biology
Background:
- Antigen-presenting cells, such as dendritic cells (DCs), play a crucial role in initiating immune responses.
- The immunomodulatory effects of all-trans retinoic acid (ATRA) on DCs are not fully understood and present some controversy.
Purpose of the Study:
- To investigate the impact of ATRA on the differentiation, maturation, and function of human monocyte-derived DCs.
- To elucidate the dose-dependent effects of ATRA on DC immunophenotype and cytokine production.
Main Methods:
- Human monocytes were differentiated into immature DCs (imDCs) or mature DCs (mDCs) with or without varying concentrations of ATRA.
- Flow cytometry was used to assess apoptosis and cell surface markers.
- Cytokine production (IL-12p40, IL-12p70, IL-10) was measured.
- T cell differentiation assays were performed.
Main Results:
- ATRA significantly increased apoptosis in both imDCs and mDCs in a dose-dependent manner.
- ATRA suppressed IL-12p40 and IL-12p70 production while increasing IL-10 production.
- ATRA-treated DCs promoted naive T cell differentiation into Th2 cells and expanded CD4(+)CD25(+)Foxp3(+) regulatory T cells.
- The allostimulatory capacity of DCs was reduced by ATRA.
Conclusions:
- ATRA inhibits the differentiation, maturation, and function of human monocyte-derived DCs in vitro.
- ATRA skews T cell differentiation towards a Th2 phenotype and enhances regulatory T cell development.

