Schematic representation of the physiological activation of NOTCH in our working model of paracrine activation of IL-6. A: JAG2 binds NOTCH via cell-to-cell contact. B: Binding of JAG2 induces a proteolytic cleavage of the intracellular part of NOTCH (N^IC). C: When cleaved, NIC is translocated into the nucleus. D: Once in the nucleus, N^IC will be able to bind to downstream effectors such as CBF1 to activate, for example, the IL-6 gene transcription.