Mechanisms of lymphocyte migration in autoimmune disease

The recruitment of leukocytes to inflamed tissues plays an essential role in combating infection and promoting wound healing. However, in autoimmune diseases such as multiple sclerosis and diabetes, leukocytes enter tissues and contribute to inappropriate inflammatory responses, which cause tissue injury and dysfunction. In diseases of this type, lymphocytes play critical roles in initiating and maintaining these aberrant inflammatory responses. The aim of this review is to examine the mechanisms whereby T-lymphocytes enter tissues in autoimmune diseases and to compare these mechanisms between various organs and diseases. An overview of the mechanisms of leukocyte recruitment and the techniques used to study leukocyte trafficking is provided, focusing on the use of intravital microscopy as a tool to assess the functional microvasculature in vivo. We also discuss the series of tissue homing events which allow naïve lymphocytes to first enter lymph nodes and undergo activation, then subsequently to home to the peripheral organ where their cognate antigen is present. Finally, we examine mechanisms of leukocyte recruitment in diseases such as multiple sclerosis, autoimmune diabetes, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease and asthma.