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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
Author(s) -
Jiang HuiRong,
Muckersie Elizabeth,
Robertson Marie,
Xu Heping,
Liversidge Janet,
Forrester John V.
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.72.5.978
Subject(s) - biology , cytokine , lipopolysaccharide , microbiology and biotechnology , dendritic cell , immunology , interleukin 4 , acquired immune system , interleukin , secretion , interleukin 10 , immune system , endocrinology
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‐γ 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.