PEPITEM
PEPITEM (Peptide Inhibitor of Trans-Endothelial Migration) is a B cell-secreted peptide which inhibits T cell trafficking across cytokine-stimulated endothelium. This homeostatic mechanism is lost in autoimmune and chronic inflammatory diseases, leading to inappropriate T cell trafficking with pathological consequences, e.g. in type-1 diabetes and rheumatoid arthritis.[1][2]
PEPITEM supplementation may represent a potential geroprotective agent to rejuvenate immune functions since it could fully restore the regulation of lymphocyte migration and thus facilitate and rejuvenate immune responses to diverse stimuli in the aged population.[3][4]
Recent efforts have identified PEPITEM (immunopeptide) for regulation of chronic inflammation in the adiponectin-PEPITEM pathway. The pathway reduced the probability of developing T2D, and fatty liver associated with obesity by enhancing leukocyte access into ATs and inducing reduced inflammatory responses in T2D and other obesity associated disorders (hepatic steatosis).[5]
PEPITEM therapy halts osteoporosis-induced bone loss and arthritis-induced bone damage in mice models of excessive bone loss and stimulates new bone formation in osteoblasts derived from patient samples.[6]
- ↑ Chimen, M., McGettrick, H. M., Apta, B., Kuravi, S. J., Yates, C. M., Kennedy, A., ... & Rainger, G. E. (2015). Homeostatic regulation of T cell trafficking by a B cell–derived peptide is impaired in autoimmune and chronic inflammatory disease. Nature medicine, 21(5), 467-475. PMID: 25894827 PMC4425550 DOI: 10.1038/nm.3842
- ↑ Apta, B. H. R. (2015). Investigating the Structure and Function of PEPITEM, a Novel Inhibitor of T cell Transmigration.
- ↑ Hopkin, S.J., Nathan, P., Pezhman, L. et al. (2024). Rejuvenation of leukocyte trafficking in aged mice through PEPITEM intervention. npj Aging 10, 33 https://doi.org/10.1038/s41514-024-00160-6
- ↑ Hopkin, S. J. (2023). PEPITEM, a regulator of leukocyte trafficking in ageing (Doctoral dissertation, University of Birmingham). https://etheses.bham.ac.uk/id/eprint/13787/
- ↑ Pezhman, L., Hopkin, S. J., Begum, J., Heising, S., Nasteska, D., Wahid, M., ... & McGettrick, H. M. (2023). PEPITEM modulates leukocyte trafficking to reduce obesity-induced inflammation. Clinical and Experimental Immunology, 212(1), 1-10. PMID: 36891817 PMC10081110 DOI: 10.1093/cei/uxad022
- ↑ Lewis, J. W., Frost, K., Neag, G., Wahid, M., Finlay, M., Northall, E. H., ... & McGettrick, H. M. (2024). Therapeutic avenues in bone repair: Harnessing an anabolic osteopeptide, PEPITEM, to boost bone growth and prevent bone loss. Cell Reports Medicine, 5(5), 101574 https://doi.org/10.1016/j.xcrm.2024.101574
