The Role of Lymphotoxin Receptor Signaling in Diseases

LT, LIGHT, and TNF are core family members of the TNFR superfamily of cytokines. LT and LIGHT, produced primarily by lymphocytes, interact with LTβR expressed by stromal and epithelial cells. Extensive studies over the last decade have revealed a critical role of LT-LTβR interactions for organogenesis and maintenance of the secondary lymphoid organs and in the generation of an efficient humoral immune response to various pathogens. LTβR's function beyond the lymphoid organs shows valuable potential yet remains largely undefined. Recent studies indicate that LTβR signaling is required for liver regeneration, hepatitis, and hepatic lipid metabolism. The balance of beneficial and detrimental effects of LTβR is critical for understanding the mechanisms of autoimmune disease and liver function and may open a new avenue for therapeutic intervention. This review will discuss recent advances in understanding LTβR's role in various human and murine disease models while focusing on its regulation of and implications in various liver related diseases.