Regulation of innate and adaptive immunity by Notch

Notch signalling has several important roles in driving both the development and function of cells of the immune system.During lymphocyte development, different Notch ligand and receptor pairs promote commitment to specific cell lineages. Delta-like ligand 4 (DLL4) interacts with Notch 1 to specify thymic T cell commitment, whereas DLL1–Notch 2 signalling promotes lineage commitment in splenic marginal zone B cells. The development of certain subsets of dendritic cells in the spleen and in the lamina propria of the intestine is also dependent on canonical Notch 2 signalling.Notch signalling influences the development and expansion of certain populations of innate lymphoid cells (ILCs), which are a recently described class of innate-like immune cells.Notch signalling is involved in T helper (TH) cell differentiation and function. DLL-mediated Notch signalling favours the development and effector functions of interferon-γ-secreting TH1 cells, whereas Jagged ligands induce the development of TH2 and regulatory T cells.Genetic, pharmacological or antibody-mediated blockade of Notch signalling can reduce the clinical severity of several mouse models of autoimmune disease.Blockade of Notch signalling in allogeneic bone marrow transplantation models inhibits pathological graft-versus-host disease while preserving beneficial graft-versus-tumour effects.This suggest that modulation of Notch signalling could be used to target immune cells during pathological conditions.