Notch signalling in the regulation of peripheral immunity

Notch signalling plays a critical role in embryogenesis, influencing the di fferentiation and growth of a variety of cell types across the species. In the mammalian immune system, Notch signalling operates at various levels; i t controls the differentiation of haematopoietic stem cells and directs the early development of the T and B-cell lineages. It is also involved in the maturation of both CD4(+) and CD8(+) T cells in the thymus. The biological activities of this pathway extend beyond lymphocyte ontogeny; recent evide nce has shown that it also contributes to the regulation of the peripheral immune system through its ability to influence cell survival and growth. In fulfilling this function, Notch signalling appears to act in conjunction w ith defined immunological signals such as cytokines, T-cell antigen recepto r and co-stimulatory receptor-mediated signalling. In this review we discus s the potential of the Notch signalling pathway in the maintenance of homeo stasis within the immune system affecting both peripheral tolerance and the negative feedback controlling productive immunity. The therapeutic manipul ation of this pathway is likely to have broad application in a range of imm unologically based diseases.