Research Paper Volume 17, Issue 3 pp 798—821
Decreased surface receptors, function, and suboptimal osteoclasts-induced cell expansion in natural killer (NK) cells of elderly subjects
- 1 Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, University of California School of Dentistry, Los Angeles, CA 90095, USA
- 2 The Jonsson Comprehensive Cancer Center, UCLA School of Dentistry and Medicine, Los Angeles, CA 90095, USA
Received: October 14, 2024 Accepted: February 19, 2025 Published: March 26, 2025
https://doi.org/10.18632/aging.206226How to Cite
Copyright: © 2025 Kaur and Jewett. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Natural killer (NK) cells are known for their cytotoxic and cytokine secretion capabilities. The balance of activating and inhibitory receptors on their surface regulates NK cell function and survival. However, it is not fully understood how aging may modulate the levels of NK cell surface receptors ultimately affecting their interaction with other immune cells, especially with those known to activate and expand NK cells. Here, we report decreased levels of NK cells’ surface receptors, cytotoxic function, and cytokine secretion in aged donors (75-85 years) as compared to younger donors (21-25 years). We used our previously established methodology to expand and supercharge NK cells from young and older individuals using osteoclasts (OCs) and probiotic bacteria. Significantly lower levels of NK cell expansion and functional activation were seen in NK cells from 75-85-year-old donors when compared to younger donors’ NK cells. Surface receptors of OCs were also found to be decreased in 75-85-year-old donors compared to younger donors. In addition, OCs from 75-85-year-old donors induced lower levels of cell expansion and functional activation of NK cells when compared to OCs from younger donors. These findings illustrate defects in both peripheral blood-derived primary NK cells and OCs in older individuals; however, suppression appears to be more in NK cells when compared to OCs.
Abbreviations
NK: Natural killer; Ocs: Osteoclasts; CSCs: Cancer stem-like cells; CD: Cluster of differentiation; IFN-γ: Interferon-gamma; TNF: Tumor necrosis factor; OSCSCs: Oral squamous carcinoma stem cells; IL: Interleukin; PBMCs: Peripheral blood mononuclear cells; KIR: Killer cell immunoglobulin like receptors; sNK: Super-charged NK.