The recombinant human TNFSF15 protein, covering residues 72-251, is generated through plasmid expression in mammalian cells. The plasmid is formed by inserting the gene segment that codes for the 72-251aa of the human TNFSF15. The gene segment is co-expressed with the N-terminal 10xHis-Avi-tag gene. The resulting TNFSF15 protein's purity is greater than 95% as accessed by SDS-PAGE. Its endotoxin content is measured to be below 1.0 EU/μg using the LAL assay. ELISA demonstrates the TNFSF15 protein's biological functionality, with specific TNFSF15 antibody (CSB-RA023992MA1HU) binding yielding an EC50 range of 0.2732 to 0.6370 ng/mL.
Human TNFSF15 (TL1A or VEGI) is a member of the TNF superfamily, with a multifaceted role in immune regulation, inflammation, and angiogenesis. TNFSF15 is primarily expressed in immune cells such as macrophages and T cells, and its expression can be induced by pro-inflammatory stimuli [1][2]. This cytokine is particularly notable for its involvement in the modulation of T-helper cell responses, especially in promoting the differentiation of Th17 cells, which are crucial in various inflammatory and autoimmune conditions [1][3][4].
TNFSF15 has been shown to inhibit angiogenesis by regulating endothelial cell proliferation and survival. It achieves this by downregulating the VEGF production and promoting apoptosis in vascular endothelial cells [2][5]. This anti-angiogenic property is significant in the context of cancer, where TNFSF15 can limit tumor growth by preventing the formation of new blood vessels [2][6]. Moreover, TNFSF15 has been implicated in various pathological conditions, including inflammatory bowel disease (IBD), where it may contribute to gut inflammation and fibrosis [3][7][8].
Recent studies have also highlighted the role of TNFSF15 in immune responses beyond inflammation. TNFSF15 has been shown to facilitate the differentiation of myeloid cells into vascular pericytes in tumors, enhancing their ability to associate with endothelial cells [9]. This suggests that TNFSF15 may have a dual role in both promoting and regulating immune responses, depending on the context [3][4]. Additionally, genetic variants of TNFSF15 have been associated with susceptibility to various diseases, including spondyloarthritis and gastric cancer, indicating its potential as a biomarker for disease risk [10][11][12].
References:
[1] M. Zucchelli, M. Camilleri, A. Andréasson, F. Bresso, A. Dlugosz, J. Halfvarson, et al. Association of tnfsf15 polymorphism with irritable bowel syndrome, Gut, vol. 60, no. 12, p. 1671-1677, 2011. https://doi.org/10.1136/gut.2011.241877
[2] P. Liang, F. Tian, Y. Lü, B. Duan, D. Stolz, & L. Li. Vascular endothelial growth inhibitor (vegi; tnfsf15) inhibits bone marrow-derived endothelial progenitor cell incorporation into lewis lung carcinoma tumors, Angiogenesis, vol. 14, no. 1, p. 61-68, 2010. https://doi.org/10.1007/s10456-010-9195-8
[3] A. Richard, J. Peters, N. Savinykh, J. Lee, E. Hawley, F. Meylan, et al. Reduced monocyte and macrophage tnfsf15/tl1a expression is associated with susceptibility to inflammatory bowel disease, Plos Genetics, vol. 14, no. 9, p. e1007458, 2018. https://doi.org/10.1371/journal.pgen.1007458
[4] J. You, J. Bian, J. Chen, T. Xia, A. Deng, M. Zhang, et al. Tnfsf15 and mia variant associated with immunotherapy and prognostic evaluation in esophageal cancer, Journal of Oncology, vol. 2023, p. 1-12, 2023. https://doi.org/10.1155/2023/1248024
[5] K. Zhang, H. Cai, S. Gao, G. Yang, H. Deng, G. Xu, et al. Tnfsf15 suppresses vegf production in endothelial cells by stimulating mir-29b expressionviaactivation of jnk-gata3 signals, Oncotarget, vol. 7, no. 43, p. 69436-69449, 2016. https://doi.org/10.18632/oncotarget.11683
[6] T. Qin, D. Huang, Z. Liu, Y. Jia, X. Chen, & K. Li. Tumor necrosis factor superfamily 15 promotes lymphatic metastasis via upregulation of vascular endothelial growth factor‐c in a mouse model of lung cancer, Cancer Science, vol. 109, no. 8, p. 2469-2478, 2018. https://doi.org/10.1111/cas.13665
[7] A. El‐Asrar, G. Hertogh, M. Nawaz, M. Siddiquei, K. Eynde, G. Mohammad, et al. The tumor necrosis factor superfamily members tweak, tnfsf15 and fibroblast growth factor-inducible protein 14 are upregulated in proliferative diabetic retinopathy, Ophthalmic Research, vol. 53, no. 3, p. 122-130, 2015. https://doi.org/10.1159/000369300
[8] D. Shih, R. Barrett, X. Zhang, N. Yeager, H. Koon, P. Phaosawasdi, et al. Constitutive tl1a (tnfsf15) expression on lymphoid or myeloid cells leads to mild intestinal inflammation and fibrosis, Plos One, vol. 6, no. 1, p. e16090, 2011. https://doi.org/10.1371/journal.pone.0016090
[9] X. Gu. Tnfsf15 facilitates the differentiation of cd11b+ myeloid cells into vascular pericytes in tumors, Cancer Biology and Medicine, p. 1-16, 2023. https://doi.org/10.20892/j.issn.2095-3941.2023.0245
[10] E. Zinovieva, C. Bourgain, A. Kadi, F. Letourneur, B. Izac, R. Said‐Nahal, et al. Comprehensive linkage and association analyses identify haplotype, near to the tnfsf15 gene, significantly associated with spondyloarthritis, Plos Genetics, vol. 5, no. 6, p. e1000528, 2009. https://doi.org/10.1371/journal.pgen.1000528
[11] Z. Zhi, D. Yu, J. Lu, K. Zhai, L. Cao, J. Rao, et al. Functional genetic variants of tnfsf15 and their association with gastric adenocarcinoma: a case-control study, Plos One, vol. 9, no. 9, p. e108321, 2014. https://doi.org/10.1371/journal.pone.0108321
[12] H. Gao, Z. Niu, Z. Zhang, H. Wu, Y. Xie, Z. Yang, et al. Tnfsf15 promoter polymorphisms increase the susceptibility to small cell lung cancer: a case-control study, BMC Medical Genetics, vol. 20, no. 1, 2019. https://doi.org/10.1186/s12881-019-0762-6
