PEPITEM
A B-cell peptide that keeps T cells out of inflamed tissue
PEPITEM, short for peptide inhibitor of trans-endothelial migration, is a 14-amino-acid peptide that B cells cut from a larger protein, 14-3-3 zeta. It tells blood vessel walls to hold back T cells during inflammation. Its levels fall with age and in type 1 diabetes and rheumatoid arthritis, and in mice adding it back calmed several inflammatory diseases and protected bone. It has not been tested as a treatment in people.
What is it?
PEPITEM was described in 2015 by a University of Birmingham group. During inflammation, and in response to the fat-derived hormone adiponectin, B cells release this peptide. It binds cadherin-15 on endothelial cells, which then release sphingosine-1-phosphate, and that signal stops T cells from crossing into tissue while leaving other white cells alone. The authors found the pathway weakens with age, and that people with type 1 diabetes or rheumatoid arthritis have less PEPITEM in their blood and lose this brake on T-cell traffic, which adding PEPITEM restored in their cells.
The animal record is broad. In the original paper it reduced T-cell recruitment in mouse models of peritonitis, liver ischaemia-reperfusion, Salmonella infection, uveitis and Sjögren's syndrome. An independent Japanese group found it shrank kidney, spleen and lymph node enlargement and reduced proteinuria in lupus-prone mice. Other studies report benefits in obesity-related inflammation, in experimental multiple sclerosis, and in aged mice, where it restored leukocyte trafficking that older adults' cells had also lost.
A second role emerged in bone. PEPITEM acts on osteoblasts through NCAM-1 to promote new bone and raises osteoprotegerin, which restrains bone-resorbing osteoclasts. In mice it halted bone loss from osteoporosis and arthritis, and it stimulated bone formation in osteoblasts from patients. Shorter fragments from both ends of the peptide reproduce some of these effects, and engineered versions reduced psoriasis severity in mice when applied to the skin.
All of this is laboratory and animal work, much of it from the group that discovered the peptide and holds patents on its use. No registered human trial appeared in what we read.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Published Research
Studies of PEPITEM, from their PubMed abstracts.
Ageing
The PEPITEM pathway lost function in older adults and aged mice, and supplementation with PEPITEM rescued leukocyte trafficking control in a mouse peritonitis model.
Bone formation
PEPITEM promoted osteoblast maturation and bone formation through NCAM-1, raised osteoprotegerin to limit osteoclasts, halted osteoporosis- and arthritis-induced bone loss in mice, and stimulated bone formation in patient-derived osteoblasts.
Lupus-prone mice
Liposomal PEPITEM for 4 weeks in MRL/lpr mice reduced kidney, spleen and lymph node enlargement, kidney T-cell infiltration, glomerular IgG/C3 deposition and proteinuria, and increased podocyte density.
Obesity-induced inflammation
In mice on a high-fat diet, PEPITEM reduced pancreatic beta-cell size, limited T-cell trafficking to visceral fat and reduced peritoneal macrophages at 6 and 12 weeks.
Fragments and psoriasis
Two tripeptide fragments and engineered peptidomimetics regulated T-cell trafficking, reduced inflammatory cells in mouse peritonitis, and, applied topically, reduced plaque psoriasis severity.
Fragments and osteoporosis
Fragments of 3 to 7 amino acids, including SVTEQGA and LSNEER, mimicked some bone effects; full-length PEPITEM or fragments spanning both ends were needed for maximal activity in ovariectomised mice.
Side Effects & Contraindications
Reported Side Effects
No human safety data exist.
Contraindications & Cautions
There is no label.
Legal Status
PEPITEM is a research peptide with no approval.
Frequently Asked Questions
?What is PEPITEM?
A natural 14-amino-acid peptide released by B cells that tells blood vessel walls to stop T cells from entering inflamed tissue. Its name stands for peptide inhibitor of trans-endothelial migration.
?Has PEPITEM been tested in humans?
Only in human blood and cells in the laboratory. People with type 1 diabetes or rheumatoid arthritis had less of it, and adding it restored T-cell control in their cells. There are no human treatment trials in what we read.
?Does PEPITEM build bone?
In mice it promoted bone formation and halted bone loss from osteoporosis and arthritis, and it stimulated bone-forming cells from patients. It has not been tested for bone in people.
?Who is developing PEPITEM?
It was discovered at the University of Birmingham, whose researchers hold patents on its use in bone and inflammatory disease and have received funding from Roche.
References
- [fda] FDA. Drugs@FDA (openFDA): no application on record for PEPITEM. Read October 3, 2026.
- [pubmed] Chimen M, et al. "Homeostatic regulation of T cell trafficking by a B cell-derived peptide is impaired in autoimmune and chronic inflammatory disease." Nat Med, 2015;21(5):467-475. PMID: 25894827.
- [pubmed] Hopkin SJ, et al. "Rejuvenation of leukocyte trafficking in aged mice through PEPITEM intervention." NPJ Aging, 2024;10(1):33. PMID: 39025913.
- [pubmed] Lewis JW, et al. "Therapeutic avenues in bone repair: Harnessing an anabolic osteopeptide, PEPITEM, to boost bone growth and prevent bone loss." Cell Rep Med, 2024;5(5):101574. PMID: 38776873.
- [pubmed] Matsubara H, et al. "PEPITEM/Cadherin 15 Axis Inhibits T Lymphocyte Infiltration and Glomerulonephritis in a Mouse Model of Systemic Lupus Erythematosus." J Immunol, 2020;204(8):2043-2052. PMID: 32169847.
- [pubmed] Pezhman L, et al. "PEPITEM modulates leukocyte trafficking to reduce obesity-induced inflammation." Clin Exp Immunol, 2023;212(1):1-10. PMID: 36891817.
- [pubmed] Saviano A, et al. "PEPITEM, its tripeptide pharmacophores and their peptidomimetic analogues regulate the inflammatory response through parenteral and topical dosing in models of peritonitis and psoriasis." Pharmacol Res, 2025;213:107624. PMID: 39855372.
- [pubmed] Frost K, et al. "PEPITEM and its tripeptide pharmacophores: Mechanisms of bone regulation and therapeutic potential in health and disease." Biomed Pharmacother, 2025;191:118489. PMID: 40876366.
Sources & Citations
Studies were read from their PubMed records, October 3, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.