TY - JOUR
T1 - Dendritic cell expression of the Notch ligand jagged2 is not essential for Th2 response induction in vivo
AU - Worsley, Alan G F
AU - LeibundGut-Landmann, Salome
AU - Slack, Emma
AU - Phng, Li Kun
AU - Gerhardt, Holger
AU - Sousa, Caetano Reis
AU - MacDonald, Andrew S.
N1 - , Cancer Research UK, United Kingdom, Medical Research Council, United Kingdom, Wellcome Trust, United Kingdom
PY - 2008/4
Y1 - 2008/4
N2 - We have addressed the hypothesis that Notch ligands play a decisive role in determining the ability of antigen-presenting cells to influence T cell polarization. Dendritic cells displayed distinct expression profiles of Delta and Jagged ligands for Notch when exposed to biologically relevant pathogen preparations associated with Th1 or Th2 responses. Expression of delta4 was increased, and jagged2 decreased, after dendritic cell exposure to the Th1-promoting bacterium Propionibacterium acnes. In contrast, soluble egg antigen (SEA) from the parasitic helminth Schistosoma mansoni, a potent Th2 inducer, failed to significantly alter dendritic cell expression of any of the Notch ligands measured. Irrespective of this, jagged2-deficient dendritic cells were severely impaired in their ability to instruct Th2 polarization of naive T cells in vitro. However, the ability of SEA-pulsed jagged2-deficient dendritic cells to induce a Th2 response in vivo was unimpaired relative to jagged2-sufficient dendritic cells. Further, jagged2-deficient dendritic cells activated by P. acnes exhibited no evidence of enhanced (or impaired) Th1 induction in vivo. These data suggest that, although involved in Th2 direction in vitro, jagged2 is not fundamentally required for Th2 induction by SEA-activated dendritic cells in vivo. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
AB - We have addressed the hypothesis that Notch ligands play a decisive role in determining the ability of antigen-presenting cells to influence T cell polarization. Dendritic cells displayed distinct expression profiles of Delta and Jagged ligands for Notch when exposed to biologically relevant pathogen preparations associated with Th1 or Th2 responses. Expression of delta4 was increased, and jagged2 decreased, after dendritic cell exposure to the Th1-promoting bacterium Propionibacterium acnes. In contrast, soluble egg antigen (SEA) from the parasitic helminth Schistosoma mansoni, a potent Th2 inducer, failed to significantly alter dendritic cell expression of any of the Notch ligands measured. Irrespective of this, jagged2-deficient dendritic cells were severely impaired in their ability to instruct Th2 polarization of naive T cells in vitro. However, the ability of SEA-pulsed jagged2-deficient dendritic cells to induce a Th2 response in vivo was unimpaired relative to jagged2-sufficient dendritic cells. Further, jagged2-deficient dendritic cells activated by P. acnes exhibited no evidence of enhanced (or impaired) Th1 induction in vivo. These data suggest that, although involved in Th2 direction in vitro, jagged2 is not fundamentally required for Th2 induction by SEA-activated dendritic cells in vivo. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
KW - Cell differentiation
KW - Dendritic cells
KW - Infectious diseases
KW - Notch signalling
KW - T helper cells
U2 - 10.1002/eji.200737335
DO - 10.1002/eji.200737335
M3 - Article
C2 - 18350543
SN - 1521-4141
VL - 38
SP - 1043
EP - 1049
JO - European journal of immunology
JF - European journal of immunology
IS - 4
ER -