Instruction of Distinct CD4 T Helper Cell Fates by Different Notch Ligands on Antigen-Presenting Cells
Copyright policy )Instruction of Distinct CD4 T Helper Cell Fates by Different Notch Ligands on Antigen-Presenting Cells
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 RBPJkappa. Notch directs Th2 differentiation by inducing GATA3 and by directly regulating il4 gene transcription through RBPJkappa sites in a 3' enhancer.
- Kyoto University Japan
- Yale University United States
- Amsterdam UMC Netherlands
- Howard Hughes Medical Institute United States
Biochemistry, Genetics and Molecular Biology(all), Calcium-Binding Proteins, Intracellular Signaling Peptides and Proteins, Antigen-Presenting Cells, Membrane Proteins, Nuclear Proteins, Cell Differentiation, Mice, Transgenic, Receptors, Cell Surface, GATA3 Transcription Factor, T-Lymphocytes, Helper-Inducer, DNA-Binding Proteins, Mice, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Animals, Intercellular Signaling Peptides and Proteins, Cell Lineage, Serrate-Jagged Proteins, Interleukin-4, Receptor, Notch1, Jagged-1 Protein
Biochemistry, Genetics and Molecular Biology(all), Calcium-Binding Proteins, Intracellular Signaling Peptides and Proteins, Antigen-Presenting Cells, Membrane Proteins, Nuclear Proteins, Cell Differentiation, Mice, Transgenic, Receptors, Cell Surface, GATA3 Transcription Factor, T-Lymphocytes, Helper-Inducer, DNA-Binding Proteins, Mice, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Animals, Intercellular Signaling Peptides and Proteins, Cell Lineage, Serrate-Jagged Proteins, Interleukin-4, Receptor, Notch1, Jagged-1 Protein
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