Immunopathologies linked to integrin signalling

Integrin binding to ligand plays essential roles in the differentiation and function of mammalian cells. beta 2 integrins in leukocytes are needed for migration to sites of inflammation and in lymph nodes as well as for cellular events such as phagocytosis and the formation of the conjugates between T cells and antigen-presenting cells. In T cells, integrin adhesion is activated primarily by the antigen-receptor (TCR complex) and chemokines in a process known as 'inside-out' signalling. Great progress has been made in identifying mutations that are responsible for leukocyte adhesion deficiency (LAD) syndromes, a disorder that presents with an impaired ability to clear pathogens and recurrent life-threatening infections. LAD mutations have been identified with defects in integrins, fucosylation and in the new intracellular mediator kindlin-3. Here, we review the key players in the 'inside-out' and 'outside-in' signalling pathways that will serve as new potential targets in the design of novel therapeutics to treat various immunodeficiencies.