@article{9d8ce98fbce34caa8fa5e8695e1eaef9,
title = "Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells",
abstract = "Antigen-presenting cells (APC) tailor immune responses to microbial encounters by stimulating differentiation of CD4 T cells into the Th1 and Th2 lineages. We demonstrate that APC use the Notch pathway to instruct T cell differentiation. Strikingly, of the two Notch ligand families, Delta induces Th1, while Jagged induces the alternate Th2 fate. Expression of these different Notch ligands on APC is induced by Th1- or Th2-promoting stimuli. Th2 differentiation has been considered a default process as APC-derived instructive signals are unknown. We demonstrate that Jagged constitutes an instructive signal for Th2 differentiation, which is independent of IL4/STAT6. Th2 differentiation induced by APC is abrogated in T cells lacking the Notch effector RBPJκ. Notch directs Th2 differentiation by inducing GATA3 and by directly regulating il4 gene transcription through RBPJκ sites in a 3′ enhancer.",
author = "Derk Amsen and Blander, {J. Magarian} and Lee, {Gap Ryol} and Kenji Tanigaki and Tasuku Honjo and Flavell, {Richard A.}",
note = "Funding Information: We gratefully acknowledge the following people for providing us with reagents: Dr. P. Marrack, Dr. L. Parreira, and Dr. M. Wolffe. We thank Dr. T. Gridley and F. Radtke for sending us RBPJκ-deficient mice and CD4-Cre transgenic mice, respectively. We thank Drs. P.E. Fields,. N. Sestan, and B. Berechid for reagents and discussion, D. Butkus for generation of transgenic mice, Tom Taylor and Gouzel Tokmulina for FACS sorting, and Fran Manzo and Ginny Chenell for secretarial support. IL12 was a gift from Wyeth Research. D.A. is an associate and R.A.F. is an investigator of the Howard Hughes Medical Institute. D.A. was supported by a NATO Talent Stipend awarded by the Dutch Organization for Scientific Research, N.W.O. ",
year = "2004",
month = may,
day = "14",
doi = "10.1016/S0092-8674(04)00451-9",
language = "English",
volume = "117",
pages = "515--526",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "4",
}