Regulation of innate and adaptive immunity by Notch.

Coordinated function of the innate and adaptive arms of the immune system in vertebrates is essential to promote protective immunity and to avoid immunopathology. The Notch signalling pathway, which was originally identified as a pleiotropic mediator of cell fate in invertebrates, has recently emerged as an important regulator of immune cell development and function. Notch was initially shown to be a key determinant of cell-lineage commitment in developing lymphocytes, but it is now known to control the homeostasis of several innate cell populations. Moreover, the roles of Notch in adaptive immunity have expanded to include the regulation of T cell differentiation and function. The aim of this Review is to summarize the current status of immune regulation by Notch. A better understanding of Notch function in both innate and adaptive immunity will hopefully provide multiple avenues for therapeutic intervention in disease.

Notch regulation of lymphocyte development and function.

Notch proteins regulate a broad spectrum of cell fate decisions and differentiation processes during fetal and postnatal development. Mammals have four Notch receptors that bind five different ligands. The function of Notch signaling during lymphopoiesis and T cell neoplasia, based on gain-of-function and conditional loss-of-function approaches for the Notch1 receptor, indicates Notch1 is essential in T cell lineage commitment. Recent studies have addressed the involvement of other Notch receptors and ligands as well as their downstream targets, demonstrating additional functions of Notch signaling in embryonic hematopoiesis, intrathymic T cell development, B cell development and peripheral T cell function.