Lymphotoxin is a member of the tumor necrosis factor (TNF) superfamily of cytokines, whose members are responsible for regulating the growth and function of lymphocytes and are expressed by a wide variety of cells in the body. Lymphotoxin plays a critical role in developing and preserving the framework of lymphoid organs and of gastrointestinal immune responses, as well as in the activation signaling of both the innate and adaptive immune responses. Lymphotoxin alpha (LT-α, previously known as TNF-beta) and lymphotoxin beta (LT-β), the two forms of lymphotoxin, each have distinctive structural characteristics and perform specific functions. Structure and function Each LT-α/LT-β subunit is a trimer and assembles into homotrimers or heterotrimers. LT-α binds with LT-β to form membrane-bound heterotrimers LT-α1-β2 and LT-α2-β1, which are commonly referred to as lymphotoxin beta. LT-α1-β2 is the most prevalent form of lymphotoxin beta. LT-α also forms a homotrimer, LT-α3, which is secreted by activated lymphocytes as a soluble protein. Lymphotoxin is produced by lymphocytes upon activation and is involved with various aspects of the immune response, including inflammation and activation signaling. Upon binding to the LTβ receptor, LT-αβ transmits signals leading to proliferation, homeostasis and activation of tissue cells in secondary lymphoid organs through induced expression of chemokines, major histocompatibility complex, and adhesion molecules. LT-αβ, which is produced by activated TH1, CD8+ T cells, and natural killer (NK) cells, is known to have a major role in the normal development of Peyer's patches. Studies have found that mice with an inactivated LT-α gene (LTA) lack developed Peyer's patches and lymph nodes. In addition, LT-αβ is necessary for the proper formation of the gastrointestinal immune system. Receptor binding and signaling activation In general, lymphotoxin ligands are expressed by immune cells, while their receptors are found on stromal and epithelial cells. The lymphotoxin homotrimer and heterotrimers are specific to different receptors. The LT-αβ complexes are the primary ligands for the lymphotoxin beta receptor (LTβR), which is expressed on tissue cells in multiple lymphoid organs, as well as on monocytes and dendritic cells. The soluble LT-α homotrimer binds to TNF receptors 1 and 2 (TNFR-1 and TNFR-2), and the herpesvirus entry mediator, expressed on T cells, dendritic cells, macrophages, and epithelial cells. There is also evidence that LTα3 signaling through TNFRI and TNFRII contributes to the regulation of IgA antibody in the gut. Lymphotoxin administers a variety of activation signals in the innate immune response. LT-α is