Inflammaging phenotype in rhesus macaques is associated with a decline in epithelial barrier-protective functions and increased pro-inflammatory function in CD161-expressing cells.

Abstract

The development of chronic inflammation, called inflammaging, contributes to the pathogenesis of age-related diseases. Although it is known that both B and T lymphocyte compartments of the adaptive immune system deteriorate with advancing age, the impact of aging on immune functions of Th17-type CD161-expressing innate immune cells and their role in inflammaging remain incompletely understood. Here, utilizing the nonhuman primate model of rhesus macaques, we report that a dysregulated Th17-type effector function of CD161+ immune cells is associated with leaky gut and inflammatory phenotype of aging. Higher plasma levels of inflammatory cytokines IL-6, TNF-α, IL-1β, GM-CSF, IL-12, and Eotaxin correlated with elevated markers of gut permeability including LPS-binding protein (LBP), intestinal fatty acid binding protein (I-FABP), and sCD14 in aging macaques. Further, older macaques displayed significantly lower frequencies of circulating Th17-type immune cells comprised of CD161+ T cell subsets, NK cells, and innate lymphoid cells. Corresponding with the increased markers of gut permeability, production of the type-17 cytokines IL-17 and IL-22 was impaired in CD161+ T cell subsets and NK cells, along with a skewing towards IFN-γ cytokine production. These findings suggest that reduced frequencies of CD161+ immune cells along with a specific loss in Th17-type effector functions contribute to impaired gut barrier integrity and systemic inflammation in aging macaques. Modulating type-17 immune cell functions via cytokine therapy or dietary interventions towards reducing chronic inflammation in inflammaging individuals may have the potential to prevent or delay age-related chronic diseases and improve immune responses in the elderly population.

• Authors: Edith M Walker, Nadia Slisarenko, Giovanni L Gerrets, Patricia J Kissinger, Elizabeth S Didier, Marcelo J Kuroda, Ronald S Veazey, S Michal Jazwinski, Namita Rout
• Journal: GeroScience (Geroscience) Vol. 41 Issue 6 Pg. 739-757 (12 2019) ISSN: 2509-2723 [Electronic] Switzerland
• PMID: 31713098 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cytokines
• NK Cell Lectin-Like Receptor Subfamily B

Topics

• Aging (immunology)
• Animals
• Chronic Disease
• Cytokines (metabolism)
• Disease Models, Animal
• Epithelium (immunology, metabolism, pathology)
• Flow Cytometry
• Immunity, Innate
• Inflammation (immunology, metabolism, pathology)
• Macaca mulatta
• NK Cell Lectin-Like Receptor Subfamily B (biosynthesis)
• Phenotype
• Th17 Cells (immunology, metabolism, pathology)