Notch ligands Delta-like1, Delta-like4 and Jagged1 differentially regulate activation of peripheral T helper cells.

摘要: The Notch pathway is involved in cell differentiation processes various organs and at several developmental stages. importance of for early T lymphocyte development well established. Recently, has been implicated directing naive helper towards the Th1, Th2 or regulatory lineages. However, molecular events underlying these are poorly understood.We show that ligands Delta-like1, Delta-like4 Jagged1 differentially affect activation proliferation following receptor cross-linking. Delta-like1 induce a dose-dependent inhibition markers CD69 CD25, as after anti-CD3 stimulation purified CD4+ cells. Similarly, rapid transcription factors NF-AT, AP-1 NF-κB suppressed. In contrast, triggering by enhances proliferation. observed effects dependent on simultaneous cross-linking TCR but independent γ-secretase-mediated cleavage Notch. These data suggest direct interference between signal transduction events, classical via release intracellular domain. A Notch-mediated alteration signaling strength may contribute to recently described modulation ligands.