Notch2 paves the way to mast cells by Hes1 and Gata3

Once regarded only as a nuisance cell that mediates allergy, mast cells (MCs) have recently gained increasing recognition as a significant regulator of the physiologic and pathologic immune response. For example, MCs not only protect the host against parasites but also play an important antibacterial role in murine models of peritonitis in which MC-deficient mice are acutely sensitive to septic shock-induced death (1, 2). Furthermore, in pathologic immune processes, MCs have been implicated in hypersensitivity and in several autoimmune diseases (3). Mast cells leave the bone marrow as committed mast cell progenitors and only undergo full maturation in target tissues. In response to certain types of inflammation, new recruitment of MC progenitors to inflamed tissues and proliferation of existing mature MCs result in robust hyperplasia of MCs in mucosal tissues. MC differentiation and expansion processes are only beginning to be characterized, and the work of Sakata-Yanagimoto et al. (4) in this issue of PNAS suggests that Notch signaling may be involved. Notch is a transmembrane receptor that regulates numerous cellular and developmental processes in multicellular organisms. Four Notch receptors (Notch1–4) and twoNotch ligand families (Delta and Jagged) have been described in mammals. Upon ligand binding, the Notch receptor undergoes cleavage, …