All-trans retinoic acid inhibits the differentiation, maturation, and function of human monocyte-derived dendritic cells.
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.
Jin
Chun-Ji
CJ
Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Jeonnam, South Korea.
Hong
Cheol Yi
CY
Takei
Masao
M
Chung
Sang-Young
SY
Park
Jung-Sun
JS
Pham
Thanh-Nhan Nguyen
TN
Choi
Soo-Jin-Na
SJ
Nam
Jong-Hee
JH
Chung
Ik-Joo
IJ
Kim
Hyeoung-Joon
HJ
Lee
Je-Jung
JJ
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D004353:Drug Evaluation, Preclinical; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D016753:Interleukin-10; D018664:Interleukin-12; D014212:Tretinoin