TY - JOUR
T1 - Suppression of Th2 cell development by Notch ligands Delta1 and Delta4
AU - Sun, Jie
AU - Krawczyk, Connie J.
AU - Pearce, Edward J.
PY - 2008/2/1
Y1 - 2008/2/1
N2 - Notch signaling plays important roles in Th cell activation. We show that in response to TLR ligation, dendritic cells up-regulate expression of Notch ligands Delta1 and Delta4 via a MyD88-dependent pathway. Expression of Delta1 or Delta4 by dendritic cells enhanced their ability to activate naive Th cells and promote Th1 cell development, and allowed them to strongly inhibit Th2 cell development. Promotion of Th1 cell development was dependent on IFN-γ and T-bet expression by responding Th cells. However, the inhibition of Th2 cell development occurred independently of IFN-γ or T-bet, and resulted from a block in IL-4-initiated commitment to the Th2 lineage. The promotion of Th1 cell development by Delta is not a reflection of the delivery of pro-Th1 instructional signal, but rather it is the result of a block in the downstream effects initiated by IL-4 signaling.
AB - Notch signaling plays important roles in Th cell activation. We show that in response to TLR ligation, dendritic cells up-regulate expression of Notch ligands Delta1 and Delta4 via a MyD88-dependent pathway. Expression of Delta1 or Delta4 by dendritic cells enhanced their ability to activate naive Th cells and promote Th1 cell development, and allowed them to strongly inhibit Th2 cell development. Promotion of Th1 cell development was dependent on IFN-γ and T-bet expression by responding Th cells. However, the inhibition of Th2 cell development occurred independently of IFN-γ or T-bet, and resulted from a block in IL-4-initiated commitment to the Th2 lineage. The promotion of Th1 cell development by Delta is not a reflection of the delivery of pro-Th1 instructional signal, but rather it is the result of a block in the downstream effects initiated by IL-4 signaling.
UR - http://www.scopus.com/inward/record.url?scp=40749089559&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=40749089559&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.180.3.1655
DO - 10.4049/jimmunol.180.3.1655
M3 - Article
C2 - 18209061
AN - SCOPUS:40749089559
SN - 0022-1767
VL - 180
SP - 1655
EP - 1661
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -