Secretion of interleukin-10 or interleukin-12 by LPS-activated dendritic cells is critically dependent on time of stimulus relative to initiation of purified DC culture.
Dendritic cells (DC) are key regulators of adaptive immunity with the potential to induce T cell activation/immunity or T cell suppression/tolerance. DC are themselves induced by "maturation" signals such as bacterial lipopolysaccharide (LPS). We demonstrate here that LPS can stimulate DC to display similar maturation phenotypes but to differentiate toward an interleukin (IL)-10(high)- or IL-12(high)-secretor profile depending on the timing of maturation signal induction. Immediate/early administration of LPS induced purified bone marrow-derived DC (BMDC) to differentiate as IL-10(high)IL-12(low)-secreting cells, termed early DC (eDC). Conversely, delayed administration of LPS altered the DC cytokine profile to IL-10(low)IL-12(high), termed later DC (lDC). The presence of IL-4 enhanced the yield and maturation of BMDC but inhibited LPS-induced IL-10 production by eDC. In contrast, interferon-gamma reduced the yield of DC but promoted the level of LPS-induced IL-10 production by lDC. Our data provide new evidence that ex vivo manipulation and the cytokine environment regulate DC maturation status and cytokine-secretor phenotype with implications for the control of T cell differentiation and function via DC-based immunotherapeutic strategies.
Jiang
Hui-Rong
HR
Department of Ophthalmology, University of Aberdeen Medical School Foresterhill, Scotland, United Kingdom.
Muckersie
Elizabeth
E
Robertson
Marie
M
Xu
Heping
H
Liversidge
Janet
J
Forrester
John V
JV
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D039521:CD11c Antigen / Q000032:analysis; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
D039521:CD11c Antigen; D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma