Lymphoid neo-organogenesis - Lymphotoxin's role in inflammation and development

Lymphoid organ development and inflammation have previously been considered as distinct mechanistically and functionally. In recent years, it has been realized that these phenomena have much in common. This insight has been g ained from the recognition that cytokines of the lymphotoxin (LT)/tumor nec rosis factor (TNF) family are involved in both processes. The members of th e family, LT-alpha, LT-beta, and TNF-alpha, and their multiple receptors pa rticipate combinatorially in lymphoid organ development and chronic inflamm ation. When inflammation that arises in microbial infection or autoimmune d isease becomes chronic, it can take on the appearance of organized lymphoid tissue and has been called a tertiary lymphoid organ. Data with transgenic and knockout mice suggest that the process is cytokine-mediated and could be called "lymphoid neo-organogenesis," LT as LT-alpha(3) and LT-alpha(1)be ta(2) plays a key role in these processes. Data obtained in vitro in an end othelial cell line and in vivo in transgenic and knockout mice indicate tha t LT influences these events through induction of adhesion molecules such a s E-selectin adhesion molecule (ELAM), vascular cell adhesion molecule (VCA M), intercellular adhesion molecule (ICAM), mucosal addressin cellular adhe sion molecule (MAdCAM), and peripheral node addressin (PNAd), and chemokine s.