TNFbeta

TNFbeta, also referred to as lymphotoxin alpha (LTα), is a cytokine belonging to the tumour necrosis factor family. It is encoded by the TNF genes situated on chromosome 6p21.31. TNFbeta is produced primarily by activated T lymphocytes, natural killer cells, and other immune cells. The protein is typically expressed as a homotrimer in soluble form, but can also exist as a membrane-bound trimer that engages in cell–cell interactions.

TNFbeta signals through two receptor complexes. The homotrimeric LTα binds the lymphotoxin β receptor (LTβR), initiating pathways that lead to NF‑κB activation and MAP kinase signalling. The heterotrimeric complex LTα1β2 recognizes tumor necrosis factor receptor 1 (TNFR1), inducing apoptosis and pro‑inflammatory gene expression. These pathways regulate apoptosis, proliferation, migration, and immune cell recruitment.

Functionally, TNFbeta plays a key role in lymphoid organ development, particularly in the formation of secondary lymphoid structures. It also contributes to immune regulation, inflammation, and host defence against pathogens. Dysregulation of TNFbeta production or signalling has been implicated in autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus. Elevated levels of the cytokine are also associated with certain cancers, where it can influence tumour growth, angiogenesis, and metastasis.

Therapeutic strategies targeting the TNFbeta pathway are under investigation. Antagonists of LTβR signalling may ameliorate chronic inflammatory conditions, while modulation of the LTα1β2/TNFR1 axis is explored for controlling tumour progression. Ongoing research continues to clarify the balance between the protective and pathological roles of TNFbeta in human disease.