TNFSF9 Specific Neutra™ Antibody Products

Tumor necrosis factor superfamily member 9 (TNFSF9), also known as 4-1BBL or CD137L, is a protein encoded by the TNFSF9 gene in humans. It is critical for immunological modulation and inflammation. Structurally, TNFSF9 is a type II transmembrane protein, with its extracellular domain containing the TNF homology domain. It functions as a co-stimulatory molecule, primarily expressed on antigen-presenting cells (APCs) like dendritic cells and macrophages. Dysregulation of TNFSF9 can impact immune homeostasis, leading to various diseases.

Its Gene ID: 8744, UniProtKB ID: P41273, and OMIM ID: 606182.

CD137/CD137L Complex

CD137, primarily expressed on activated T cells, binds with its ligand CD137L to form CD137/CD137L complex. This interaction occurs between the TNF receptor superfamily domain of CD137 and the TNF homology domain of CD137L. The complex consists of three monomeric CD137s bound to a trimeric CD137L. Each CD137 monomer binds to two CD137Ls via cysteine-rich domains (CRDs). The non-covalent interactions between the trimeric forms of CD137 and CD137L maintain the stability of the complex. Functionally, the CD137/CD137L complex acts as a co-stimulatory pathway, enhancing T cell activation, proliferation, and survival. This complex plays a pivotal role in regulating immune responses, particularly in tumor immunity, autoimmunity, and infectious diseases, making it a target for immunotherapy interventions.

CD137L Reverse Signal Transduction Pathways

CD137L, upon binding to its receptor CD137, initiates reverse signal transduction pathways in APCs. This triggers intracellular signaling cascades, notably NF-κB, MAPK, and PI3K/Akt. The activation of NF-κB induces transcription of genes implicated in inflammation and immune response regulation. MAPK pathways, including ERK, JNK, and p38, regulate cell proliferation, survival, and cytokine production in APCs. The PI3K/Akt pathway enhances APC survival and promotes cell growth and metabolism. Additionally, CD137L reverse signaling augments antigen presentation by upregulating MHC molecules and co-stimulatory molecules like CD80 and CD86. Collectively, these cascades bolster APC function, shaping adaptive immune responses and influencing T cell activation and differentiation in various physiological and pathological conditions.

Fig.1 Signaling pathways mediating signal transduction of CD137 and CD137L.¹

Antibodies Targeting CD137L

Research on antibodies targeting CD137L has focused on two main types: agonistic and antagonist antibodies. Agonistic antibodies bind to CD137L, mimicking the effects of CD137 engagement, thereby enhancing T cell activation, proliferation, and effector functions. These antibodies hold promise for cancer immunotherapy, augmenting anti-tumor immune responses. In contrast, antagonist antibodies block the interaction between CD137L and its receptor CD137, inhibiting co-stimulatory signaling. This approach may be beneficial in autoimmune diseases and inflammatory conditions, where dampening excessive immune activation is desirable. For instance, one antagonistic anti-CD137L antibody has been shown to reduce collagen-induced arthritis and LPS-induced sepsis.

Fig.2 Immune modulation with CD137L agonist.²

Creative Biolabs offers thirteen high-quality anti-TNFSF9 (CD137L) antibody products that can be used in several applications to assist you in effectively completing your research projects.

REFERENCES

1. Mak, Anselm, and Herbert Schwarz. "The progress of investigating the CD137-CD137L axis as a potential target for systemic lupus erythematosus." Cells 8.9 (2019): 1044. Distributed under Open Access license CC BY 4.0, without modification.
2. Choi, Beom K., and Hyeon-Woo Lee. "The murine CD137/CD137 ligand signalosome: A signal platform generating signal complexity." Frontiers in immunology 11 (2020): 553715. Distributed under Open Access license CC BY 4.0, without modification.