Abstract
Natural killer (NK) lymphocyte-mediated cytotoxicity and cytokine secretion control infections and cancers, but these crucial activities decline with age. NK cell development, homeostasis, and function require IL-15 and its chaperone, IL-15 receptor alpha (IL-15Rα). Macrophages and dendritic cells (DC) are major sources of these proteins. We had previously postulated that additional IL-15 and IL-15Rα is made by skeletal muscle and adipose tissue. These sources may be important in aging, when IL-15-producing immune cells decline. NK cells circulate through adipose tissue, where they may be exposed to local IL-15. The objectives of this work were to determine (1) if human muscle, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) are sources of IL-15 and IL-15 Rα, and (2) whether any of these tissues correlate with NK cell activity in elderly humans. We first investigated IL-15 and IL-15Rα RNA expression in paired muscle and SAT biopsies from healthy human subjects. Both tissues expressed these transcripts, but IL-15Rα RNA levels were higher in SAT than in skeletal muscle. We also investigated tissue obtained from surgeries and found that SAT and VAT expressed equivalent amounts of IL-15 and IL-15Rα RNA, respectively. Furthermore, stromal vascular fraction cells expressed more IL-15 RNA than did adipocytes. To test if these findings related to circulating IL-15 protein and NK cell function, we tested 50 healthy adults aged > 70 years old. Plasma IL-15 levels significantly correlated with abdominal VAT mass in the entire cohort and in non-obese subjects. However, plasma IL-15 levels did not correlate with skeletal muscle cross-sectional area and correlated inversely with muscle strength. Plasma IL-15 did correlate with NK cell cytotoxic granule exocytosis and with CCL4 (MIP-1β) production in response to NKp46-crosslinking. Additionally, NK cell responses to K562 leukemia cells correlated inversely with muscle strength. With aging, immune function declines while infections, cancers, and deaths increase. We propose that VAT-derived IL-15 and IL-15Rα is a compensatory NK cell support mechanism in elderly humans.
Document Type
Article
Publication Date
3-6-2018
Digital Object Identifier (DOI)
https://doi.org/10.3389/fimmu.2018.00440
Funding Information
This work was supported by NIH grants, AG040542, AG049806, DK107646, DK071349, and UL1TR001998.
Related Content
The Supplementary Material for this article can be found online at http://www.frontiersin.org/articles/10.3389/fimmu.2018.00440/full#supplementary-material.
Repository Citation
Al-Attar, Ahmad; Presnell, Steven R.; Clasey, Jody L.; Long, Douglas E.; Walton, R. Grace; Sexton, Morgan; Starr, Marlene E.; Kern, Philip A.; Peterson, Charlotte A.; and Lutz, Charles T., "Human Body Composition and Immunity: Visceral Adipose Tissue Produces IL-15 and Muscle Strength Inversely Correlates with NK Cell Function in Elderly Humans" (2018). Pathology and Laboratory Medicine Faculty Publications. 28.
https://uknowledge.uky.edu/pathology_facpub/28
Supplementary Material
Included in
Cell and Developmental Biology Commons, Musculoskeletal System Commons, Pathology Commons
Notes/Citation Information
Published in Frontiers in Immunology, v. 9, article 440, p. 1-11.
© 2018 Al-Attar, Presnell, Clasey, Long, Walton, Sexton, Starr, Kern, Peterson and Lutz.
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