TNFSF4 Specific Neutra™ Antibody Products

Product list

TNFSF4 (TNF Superfamily Member 4), also known as OX40 ligand (OX40L), belongs to the TNF superfamily. It is a type II transmembrane protein with a cytoplasmic tail of 23 amino acids and a 133-amino acid extracellular domain. OX40L binds to its receptor, OX40, on activated T cells, triggering co-stimulatory signals essential for T cell survival, proliferation, and cytokine production. This interaction plays a crucial role in regulating immune responses, particularly in the activation and maintenance of effector T cells. OX40L is pivotal in adaptive immunity and inflammatory processes.

Its Gene ID: 7292, UniProtKB ID: P23510, and OMIM ID: 603594.

Expressions of OX40L

OX40L expression is tightly regulated, primarily occurring on antigen-presenting cells such as macrophages, dendritic cells, and B cells upon activation by microbial stimuli or cytokines. Additionally, OX40L expression can be induced on endothelial cells, fibroblasts, and smooth muscle cells in inflammatory conditions. Notably, OX40L expression is upregulated in various immune-mediated disorders, including autoimmune diseases and allergic responses, indicating its involvement in pathogenesis. Conversely, its expression can be downregulated by regulatory T cells and anti-inflammatory cytokines, serving as a feedback mechanism to modulate immune responses and maintain immune homeostasis.

Effects of the OX40–OX40L Interaction

The OX40-OX40L interaction orchestrates a balanced immune response by regulating various T cell subsets and B cells. In effector CD4⁺ T cells, engagement of OX40 by OX40L enhances cell survival, proliferation, and cytokine production, promoting the development of T helper cell responses, particularly Th1 and Th2 subsets. OX40-OX40L interaction also reinforces the differentiation and maintenance of memory CD4⁺ T cells, which is crucial for long-term immunity. Additionally, in CD8⁺ cytotoxic T cells, this interaction enhances effector function and memory formation, augmenting cellular immune responses against pathogens and tumors. Moreover, the OX40-OX40L axis influences regulatory T cells (Tregs), attenuating their suppressive activity and promoting their proliferation, which can modulate immune tolerance and autoimmunity. In B cells, OX40 signaling enhances antibody production, class-switching, and memory B cell formation, contributing to humoral immune responses.

Fig.1 Role of OX40-OX40L signaling in immune response. Fig.1 OX40-OX40L signaling stimulates effector T cell proliferation, resulting in an initial immunological response.¹

Roles of OX40L in Cancer and Autoimmune Disease

In cancer, OX40L, expressed by antigen-presenting cells and tumor cells, interacts with OX40 on T cells, promoting tumor immunity. For instance, in breast carcinomas, OX40L/OX40 interaction enhances T cell activation, cytokine secretion, and cytotoxicity, inhibiting tumor growth. Similarly, in melanoma, OX40L engagement boosts anti-tumor immunity, suppressing tumor progression and metastasis. Conversely, in autoimmune diseases like rheumatoid arthritis and lupus, dysregulated OX40L signaling exacerbates inflammation and tissue damage. OX40L-mediated activation of autoreactive T cells and B cells leads to the production of autoantibodies and inflammatory cytokines, perpetuating autoimmune responses. Targeting OX40L shows promise in both cancer immunotherapy and autoimmune disease management, modulating immune dysregulation for therapeutic benefit.

Antibodies Targeting OX40L

Antibodies targeting OX40L block the interaction between OX40L and its receptor OX40, inhibiting downstream T-cell activation and cytokine production. Research indicates the potential of agonist antibodies in cancer immunotherapy by enhancing anti-tumor immunity and promoting tumor regression. Additionally, in autoimmune diseases, OX40L blockade attenuates aberrant T cell activation and autoantibody production, ameliorating disease progression. Clinical studies demonstrate promising outcomes, with some antibodies showing efficacy and safety profiles in preclinical and early-phase trials.

Fig.2 Novel monoclonal antibody treatments targeting the OX40-OX40L interaction. Fig.2 Novel therapies of monoclonal antibodies targeting the interaction between OX40 and OX40L.¹

Creative Biolabs offers nearly thirty different types of high-quality anti-TNFSF4 antibody products that can be used for thirteen different applications to meet your various research needs.

REFERENCE

Sadrolashrafi, Kaviyon, et al. "An OX-Tra’Ordinary Tale: The Role of OX40 and OX40L in Atopic Dermatitis." Cells 13.7 (2024): 587. Distributed under Open Access license CC BY 4.0, without modification.

Show More Close