Phosphoinositide 3-kinase delta (PI3Kδ) in leukocyte signaling and function

PI3K delta is a lipid kinase of the PI3K class IA family involved in early signaling events of leukocytes responding to a wide variety of stimuli. The leukocyte specificity of PI3K delta is defined by its expression, whereas its signaling function is via the production of phosphoinositide 3,4,5-triphosphates at the proximity of activated receptors for recruiting other signaling molecules. The importance of PI3K delta in B cell development and function is most apparent, and its role in other leukocyte cell types can be easily demonstrated as well. PI3K delta participates in the development, activation and migration of T cells and NK cells. The role of PI3K delta in myeloid cell activities, such as inflammation driven cell infiltration, neutrophil oxidative burst, immune complex mediated macrophage activation, as well as mast cell maturation and degranulation, has been well illustrated in various studies. As a result of the broad effects of PI3K delta in leukocyte functions, the disruption of PI3K delta expression or activity leads to decreased inflammatory and immune responses in vivo. The protective role of PI3K delta inactivation in animal models of arthritis, asthma or obstructive respiratory diseases has been demonstrated. These findings suggest the potential efficacy achievable with PI3K delta inhibitors in the treatment of autoimmune and respiratory diseases. (C) 2010 Elsevier Inc. All rights reserved.