Researchers here describe an injected immunomodulatory peptide that reduces migration of adaptive immune cells in response to inflammatory signaling. They mount the argument that excessive immune cell migration is a sizable part of the problem in the chronic inflammation of aging, and arises due to age-related changes in immune cell behavior. Delivering the peptide is intended to restore a more youthful regulation of this immune cell behavior.
Growing evidence suggests that the ageing process significantly impacts leukocyte trafficking dynamics during inflammation, thereby compromising protective immunity. We have previously reported that ageing increases homeostatic leukocyte trafficking to the peritoneal cavity in mice through pro-inflammatory mediators and enhanced vascular permeability. Whilst ageing increases neutrophil and monocyte trafficking in response to peritonitis, patterns of lymphocyte trafficking are still unknown in this model.
Here, we investigated how ageing changes leukocyte trafficking dynamics and the impact of a novel immunopeptide (PEPITEM) has on this using an inflammation model of zymosan-induced peritonitis in young (3-month) and aged (21-month) male mice. Zymosan-induced peritonitis typically represents a simplified model of the disease, focusing primarily on the early inflammatory events. It may not adequately capture the later stages of human peritonitis development, including tissue damage and organ dysfunction. Nonetheless, it remains a highly reproducible and robust model, characterised by significant recruitment of various immune cells.
We previously identified PEPITEM as a key regulator of leukocyte trafficking. Indeed, through action of adiponectin on its receptors (AdipoR1 and AdipoR2) on B-cells, PEPITEM is released to then stimulate endothelial production of spingosine-1-phosphate (S1P). S1P will in turn inhibit leukocyte trafficking through modulation on integrin signalling. We analysed whether intraperitoneal injection of PEPITEM could modulate leukocyte migration in older mice. We observed a loss of functionality in the PEPITEM pathway, which normally controls leukocyte trafficking in response to inflammation, in older adults and aged mice and show that this can be rescued by supplementation with PEPITEM. Thus, leading to the exciting possibility that PEPITEM supplementation may represent a potential pre-habilitation geroprotective agent to rejuvenate immune functions.
Link: https://doi.org/10.1...514-024-00160-6
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