Rapamycin-treated mature dendritic cells have a unique cytokine secretion profile and impaired allostimulatory capacity.
Rapamycin (RAPA, sirolimus) is a recently introduced immunosuppressive agent. Its effect on the differentiation and antigen uptake of immature dendritic cells (iDCs) has been studied. However, whether it can also modulate the function of mature DCs (mDCs) is unknown. We investigated the effects of RAPA on rat bone marrow-derived DCs at different stages of maturation. RAPA affected maturation, increased apoptosis and reduced lipopolysaccharide (LPS)-induced IL-12 and IL-10 production in iDCs. However, mDCs were resistant to RAPA-induced apoptosis. RAPA-mDCs produced significantly less IL-10 and TNF-alpha when compared with mature DCs but similar amounts of IL-12. RAPA did not affect constitutive NF-kappaB activity, but inhibited allostimulatory activity in mature DCs. In conclusion, mDCs treated with RAPA are reprogrammed to produce a unique cytokine secretion profile and exhibit low allostimulatory capacity, which may play an important role in rapamycin-based immunomodulation.
Wang
Guo-Ying
GY
Institute of Organ Transplantation, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Chen
Gui-Hua
GH
Li
Hua
H
Huang
Yong
Y
Wang
Gen-Shu
GS
Jiang
Nan
N
Fu
Bin-Sheng
BS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051940:B7-2 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D020123:Sirolimus / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D051940:B7-2 Antigen; D019013:CD40 Antigens; C497966:Cd86 protein, rat; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D020123:Sirolimus