Inflammaging phenotype in rhesus macaques is associated with a decline in epithelial barrier-protective functions and increased pro-inflammatory function in CD161-expressing cells
| Autor: | Namita Rout, Ronald S. Veazey, Elizabeth S. Didier, Edith M. Walker, S. Michal Jazwinski, Patricia Kissinger, Marcelo J. Kuroda, Nadia Slisarenko, Giovanni L. Gerrets |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Aging
1.1 Normal biological development and functioning medicine.medical_treatment T cell CD161+cells Inflammation CD161+ cells Biology Systemic inflammation Epithelium I-FABP Immune system Underpinning research LBP medicine Animals Innate 2.1 Biological and endogenous factors Aetiology Innate immune system Animal Inflammatory and immune system Innate lymphoid cell Immunity Correction Flow Cytometry sCD14 Acquired immune system Macaca mulatta Inflammaging Immunity Innate Disease Models Animal Phenotype Cytokine medicine.anatomical_structure Leaky gut Disease Models Chronic Disease Immunology Cytokines Th17 Cells HIV/AIDS Original Article Geriatrics and Gerontology medicine.symptom NK Cell Lectin-Like Receptor Subfamily B |
| Zdroj: | GeroScience, vol 41, iss 6 |
| ISSN: | 2509-2723 2509-2715 |
| DOI: | 10.1007/s11357-019-00099-7 |
| Popis: | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11357-019-00099-7) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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