LTA

Official Full Name

lymphotoxin alpha

Organism

Homo sapiens

GeneID

4049

Background

The encoded protein, a member of the tumor necrosis factor family, is a cytokine produced by lymphocytes. The protein is highly inducible, secreted, and forms heterotrimers with lymphotoxin-beta which anchor lymphotoxin-alpha to the cell surface. This protein also mediates a large variety of inflammatory, immunostimulatory, and antiviral responses, is involved in the formation of secondary lymphoid organs during development and plays a role in apoptosis. Genetic variations in this gene are associated with susceptibility to leprosy type 4, myocardial infarction, non-Hodgkin's lymphoma, and psoriatic arthritis. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

Synonyms

LT; TNFB; TNFSF1; TNLG1E;

Bio Chemical Class

Cytokine: tumor necrosis factor

Protein Sequence

MTPPERLFLPRVCGTTLHLLLLGLLLVLLPGAQGLPGVGLTPSAAQTARQHPKMHLAHSTLKPAAHLIGDPSKQNSLLWRANTDRAFLQDGFSLSNNSLLVPTSGIYFVYSQVVFSGKAYSPKATSSPLYLAHEVQLFSSQYPFHVPLLSSQKMVYPGLQEPWLHSMYHGAAFQLTQGDQLSTHTDGIPHLVLSPSTVFFGAFAL

Open

Disease

Rheumatoid arthritis

Approved Drug

Clinical Trial Drug

1 +

Discontinued Drug

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Detailed Information

In 1975, Carswell et al. discovered that when BCG-vaccinated mice were injected with LPS, their serum contained a factor capable of killing certain tumor cells or causing hemorrhagic necrosis in tumor tissues, which they termed tumor necrosis factor (TNF). In 1985, Shalaby designated TNF produced by macrophages as TNF-α, while lymphotoxin (LT) produced by T lymphocytes was renamed TNF-β.

The LTA gene is located on the short arm of human chromosome 6 (6p21.3), near the Major Histocompatibility Complex (MHC) region. This gene encodes a protein consisting of 171 amino acids with a molecular weight of approximately 25 kDa. The LTA protein can form soluble homotrimers (LT-α3) or heterotrimers with lymphotoxin β (LT-α1β2), with the latter anchored to the cell membrane. This structural diversity enables LTA to perform multiple functions in various physiological and pathological processes.

LTA is primarily expressed in activated T cells, B cells, and natural killer cells. According to the Human Protein Atlas, LTA expression is highest in lymph nodes, appendix, and other immune-related tissues. Its expression is regulated by various cytokines and signaling pathways, including IL-2, IL-12, and NF-κB.

Diagram showing LTα, LIGHT, and LTβ interacting with their receptors LTβR, HVEM, and TNFR, including immune modulators CD160 and BTLA, indicating both membrane-bound and soluble cytokine forms and their signaling pathways. Figure 1. Schematic illustration of receptor-ligand interactions among the LT/LIGHT cytokine family and their corresponding receptors. (Lu TT, et al., 2014)

Functions of LTA

Immune Regulation: LTA performs multiple roles within the immune system. Its soluble homotrimeric form (LT-α3) primarily binds to TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2), activating downstream signaling pathways such as NF-κB and MAPK, which regulate inflammatory factor expression, cell proliferation, and apoptosis. The membrane-bound heterotrimeric form (LT-α1β2) interacts with lymphotoxin β receptor (LTβR), participating in the development and maintenance of secondary lymphoid organs.

Development of Secondary Lymphoid Organs: LTA plays a critical role in the development of secondary lymphoid organs (such as lymph nodes, spleen, and Peyer's patches). Studies have shown that LTA-deficient mice lack normal lymph nodes and Peyer's patches, and exhibit abnormal splenic structure. This indicates that LTA, through the LTβR signaling pathway, induces the expression of chemokines and adhesion molecules, promoting lymphoid tissue formation and establishing tissue architecture.

Inflammation and Apoptosis: LTA induces inflammatory factor expression and cell apoptosis by activating TNFR1 and TNFR2. It shares similar functions with TNF, though in certain circumstances, LTA's effects are more pronounced. Research has found that LTA has comparable potency to TNF in inducing apoptosis and necroptosis. Additionally, LTA can further regulate immune and inflammatory responses through heterotrimers formed with LTβ that activate LTβR.

LTA and Disease Associations

Leprosy: Certain variants of the LTA gene are associated with susceptibility to leprosy. Studies indicate that LTA gene polymorphisms may affect individual immune responses to Mycobacterium leprae infection, thereby influencing disease progression.

Myocardial Infarction: LTA gene variants are also associated with increased risk of myocardial infarction. Certain LTA gene polymorphisms may influence atherosclerosis progression by regulating inflammatory responses, thereby increasing myocardial infarction risk.

Non-Hodgkin Lymphoma: LTA gene variations are associated with increased risk of Non-Hodgkin Lymphoma (NHL). Research has found that the LTA 252A>G allele is associated with increased risk of Diffuse Large B-Cell Lymphoma (DLBCL). These variants may affect lymphoma development by influencing LTA expression or function, regulating immune responses and cell apoptosis.

Psoriatic Arthritis: LTA gene variants are also associated with susceptibility to psoriatic arthritis. Certain LTA gene polymorphisms may affect joint inflammation and destruction processes by regulating inflammatory responses, thereby increasing psoriatic arthritis risk.

Role of LTA in Cancer

Anti-tumor Effects: LTA exhibits anti-tumor properties. Its soluble homotrimeric form can induce tumor cell apoptosis and inhibit tumor growth. Additionally, LTA can enhance immune surveillance and clearance of tumors by activating immune cells.

Pro-tumor Effects: However, LTA may also exhibit pro-tumor effects. In certain circumstances, persistent LTA expression may lead to chronic inflammation, promoting tumor initiation and progression. For example, studies have found that mice overexpressing LTA show increased tumor growth and metastasis in certain cancer models. This suggests that LTA plays a dual role in tumors, capable of both inhibiting and potentially promoting tumorigenesis.

References

Calmon-Hamaty F, Combe B, Hahne M, et al. Lymphotoxin α revisited: general features and implications in rheumatoid arthritis. Arthritis Res Ther. 2011 Jul 26;13(4):232.
Paik B, Tong L. Polymorphisms in Lymphotoxin-Alpha as the "Missing Link" in Prognosticating Favourable Response to Omega-3 Supplementation for Dry Eye Disease: A Narrative Review. Int J Mol Sci. 2023 Feb 20;24(4):4236.
Lu TT, Browning JL. Role of the Lymphotoxin/LIGHT System in the Development and Maintenance of Reticular Networks and Vasculature in Lymphoid Tissues. Front Immunol. 2014;5:47.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry