Artificial phosphatidylserine liposome mimics apoptotic cells in inhibiting maturation and immunostimulatory function of murine myeloid dendritic cells in response to 1-chloro-2,4-dinitrobenze in vitro.
Phosphatidylserine (PS) exposed on the apoptotic cell surface inhibits inflammatory responses, implying that PS may regulate the function of dendritic cells (DCs) after being phagocytosed by the latter. Here we use PS liposomes to investigate the effects of PS on the maturation and immunostimulatory functions of DCs in response to the challenge of 1-chloro-2,4-dinitrobenze (DNCB) in vitro. We demonstrate that after treatment with PS, murine DCs display reduced expression of MHC II, CD80, CD86 and CD40, but increased programmed death ligand-1 (PD-L1 and PD-L2); and increased IL-10 and inhibited IL-12 cytokine production. PS-treated DCs exhibit normal endocytic function, but ability to stimulate allogeneic T cells is reduced, similar to immature dendritic cell (iDCs). Treatment of DCs with PS liposomes also suppressed DNCB induced CD4 + T cell proliferation and IFN-gamma production. Addition of exogenous IL-12p70 during the DC-T cell co-culture restored their IFN-gamma production. Furthermore, PS-treated DCs enhance the ratio of CD4(+) CD25(high)Foxp3(+) T cells to CD4(+) T cells and PD-1 expression on CD4(+) T cells. These data demonstrate that PS liposomes have therapeutic potential in allergic contact dermatitis (ACD).
Shi
Dongmei
D
Dermatology Center of Chinese PLA, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Fu
Meng
M
Fan
Pinshen
P
Li
Wei
W
Chen
Xinhui
X
Li
Chenxin
C
Qi
Xianlong
X
Gao
Tianwen
T
Liu
Yufeng
Y
D000818:Animals; D017209:Apoptosis; D018122:B7-1 Antigen / Q000502:physiology; D060890:B7-H1 Antigen; D003713:Dendritic Cells / Q000502:physiology*; D004137:Dinitrochlorobenzene / Q000494:pharmacology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008081:Liposomes / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000502:physiology*; D010455:Peptides / Q000502:physiology; D010718:Phosphatidylserines / Q000494:pharmacology*; D061027:Programmed Cell Death 1 Ligand 2 Protein; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D004137:Dinitrochlorobenzene; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D008081:Liposomes; D008562:Membrane Glycoproteins; C556978:Pdcd1lg2 protein, mouse; D010455:Peptides; D010718:Phosphatidylserines; D061027:Programmed Cell Death 1 Ligand 2 Protein; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma