Lymphotoxin alpha and Lymphotoxin beta are pro-inflammatory TNF superfamily ligands that play important roles in immune system development. LT-alpha can be secreted as a homotrimer that binds and activates TNF RI, TNF RII, HVEM, and TROY. It is required for development of the spleen, lymph nodes, and Peyerâs patches. It also regulates T cell homing to the gut and IgA induction. LT-alpha can additionally form membrane-associated heterotrimers with two copies of LT-beta/TNF-beta on the surface of B, T, LTi, and ILC3 cells. This heterotrimer binds and activates the Lymphotoxin beta R on macrophages, dendritic cells, hepatocytes, intestinal epithelial cells (IEC), follicular dendritic cells (FDC), and high endothelial venules (HEV). The heterotrimer promotes the development of FDC networks and HEV in lymphoid tissue, the class switching of immature B cells for IgA production, and the production of homeostatic IL-22 by IEC.