Introduction

• Lymphotoxin Alpha (LT-α), also known as Tumor Necrosis Factor-β (TNF-β), is a cytokine involved in immune system development, inflammation, and host defence mechanisms.
• Produced by the LTA gene, it is a member of the tumor necrosis factor (TNF) superfamily.
• Extensive research on LT-α has led to the development of new therapeutic approaches for immune-mediated diseases.

Molecular Structure and Expression

• Two main forms: secreted homotrimer (LT-α3) and membrane-anchored heterotrimer (LT-α1β2) when bound to lymphotoxin beta.
• Synthesized by T lymphocytes, B cells, NK cells, and lymphoid tissue inducer cells after activation.
• Expression regulated by various stimuli such as inflammatory mediators and cytokines.
• Can bind to multiple receptors (TNFR1 and TNFR2), initiating several intracellular signalling pathways.

Biological Functions and Signalling Pathways

• Essential for immune system development and function:
• Lymphoid Organ Development:
• Formation and organization of secondary lymphoid organs.
• Development of lymph nodes and Peyer's patches.
• Maintenance of spleen and lymph node architecture.
• Immune Response Regulation:
• Mediates inflammatory responses.
• Promotes production of cytokines and chemokines.
• Facilitates immune cell recruitment and activation.
• Supports germinal centre formation and antibody responses.
• Host Defence:
• Protection against viral infections.
• Supports immune responses against intracellular pathogens.
• Enhances natural killer cell activity.
• Activates; NF-κB and other transcription factors, influencing cell survival, proliferation, and inflammatory responses.

Role in Disease and Pathological Conditions

• Implicated in various pathological conditions:
• Autoimmune Disorders: Multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease.
• Inflammatory Conditions: Chronic inflammation, tissue damage, fibrosis.
• Cancer: Tumor development and progression, anti-tumor immune responses, metastasis.
• Understanding its role has led to targeted therapies and therapeutic strategies.

Therapeutic Applications and Clinical Significance

• Extensive studies have led to several clinical applications:
• Development of specific antibodies targeting LT-α.
• Design of receptor antagonists.
• Creation of fusion proteins to modulate LT-α signalling.
• Clinical applications include:
• Autoimmune disease management.
• Cancer immunotherapy.
• Inflammatory disorder treatment.
• Transplant rejection prevention.