LTBR Human

The Lymphotoxin Beta Receptor (LTβR) is a member of the tumor necrosis factor receptor (TNFR) superfamily. It plays a crucial role in the development and maintenance of secondary lymphoid organs, such as lymph nodes and Peyer’s patches, and is involved in immune cell homeostasis .

LTβR is a type 1 single transmembrane protein. It is primarily known for its role in regulating immune responses and inflammation. Upon ligand binding, LTβR activates several signaling pathways, including the pro-inflammatory NF-κB and AP-1 pathways . This receptor is predominantly present on endocytic vesicles and the Golgi apparatus, and its internalization is crucial for regulating its signaling potential .

LTβR signaling is essential for the organization and maintenance of lymphoid organs. In the spleen, it is required for the development of B cell follicles, follicular dendritic cells (FDCs), and the recruitment of neutrophils . In lymph nodes, LTβR signaling maintains the structure and function of subcapsular sinus macrophages and FDCs . Additionally, LTβR is involved in the homeostasis of neutrophils, NK cells, and iNKT cells .

Upon activation by its ligands, LTβR triggers the canonical and non-canonical NF-κB pathways. The receptor’s internalization, which is clathrin- and dynamin-dependent, limits the activation of the canonical NF-κB signaling . This internalization process ensures that the receptor’s signaling is tightly regulated and prevents excessive inflammatory responses .

The regulation of LTβR signaling involves its endocytosis and trafficking to lysosomes for degradation. This process is crucial for maintaining the balance between receptor activation and inhibition . Additionally, LTβR signaling is modulated by various intracellular proteins that control its endocytic routes and signaling cascades .

LTβR is a promising therapeutic target for autoimmune and infectious diseases, as well as cancer. Mice with genetic inactivation of LTβR display multiple defects in the development and organization of lymphoid organs, mucosal immune responses, and IgA production . Understanding the role of LTβR in these processes can lead to the development of novel therapeutic strategies for various diseases.