TY - JOUR
T1 - IL10 and IL12B polymorphisms each influence IL-12p70 secretion by dendritic cells in response to LPS
AU - Peng, J.C.
AU - Abubakar, S.
AU - Richardson, M.M.
AU - Jonsson, J.J.
AU - Frazer, I.H.
AU - Nielsen, L.K.
AU - Morahan, Grant
AU - Thomas, R.
PY - 2006
Y1 - 2006
N2 - Dendritic cells (DC) are the main producers of the cytokine IL-12p70, through which they play a direct role in the development of IFN-gamma-secreting Th1 cells, costimulation of CTL differentiation and NK-cell activation. In contrast, IL-10, which is also produced by DC, negatively regulates IL-12 production. IL-12p70 production varies widely between individuals, and several polymorphisms in the gene encoding IL-12p40 (IL12B) have been identified that influence susceptibility and severity of infectious, autoimmune and neoplastic disease. Here we show that polymorphisms not only of IL12B, but also in the IL10 promoter, influence IL-12p70 secretion by monocyte-derived DC in response to LPS. Although IL12B promoter homozygotes were prone to making more IL-12p70, presence of the IL10 high genotype restricted IL-12p70 production in these individuals. These observations provide a further genetic control of IL-12p70 regulation and emphasize the complexity of production of this cytokine. They also suggest genotypes that might influence the outcome of DC immunotherapy.
AB - Dendritic cells (DC) are the main producers of the cytokine IL-12p70, through which they play a direct role in the development of IFN-gamma-secreting Th1 cells, costimulation of CTL differentiation and NK-cell activation. In contrast, IL-10, which is also produced by DC, negatively regulates IL-12 production. IL-12p70 production varies widely between individuals, and several polymorphisms in the gene encoding IL-12p40 (IL12B) have been identified that influence susceptibility and severity of infectious, autoimmune and neoplastic disease. Here we show that polymorphisms not only of IL12B, but also in the IL10 promoter, influence IL-12p70 secretion by monocyte-derived DC in response to LPS. Although IL12B promoter homozygotes were prone to making more IL-12p70, presence of the IL10 high genotype restricted IL-12p70 production in these individuals. These observations provide a further genetic control of IL-12p70 regulation and emphasize the complexity of production of this cytokine. They also suggest genotypes that might influence the outcome of DC immunotherapy.
UR - https://www.scopus.com/pages/publications/33644783595
U2 - 10.1111/j.1440-1711.2006.01419.x
DO - 10.1111/j.1440-1711.2006.01419.x
M3 - Article
C2 - 16519741
SN - 0818-9641
VL - 84
SP - 227
EP - 232
JO - Immunology and Cell Biology
JF - Immunology and Cell Biology
IS - 2
ER -