Cited by 106Chronic Obstructive Pulmonary Disease (COPD) ResearchAsthma and respiratory diseasesSmoking Behavior and Cessation

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The Aging Immune System and Its Relationship to the Development of Chronic Obstructive Pulmonary Disease

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Sharma, Gulshan, Hanania, Nicola A., Shim, Y. Michael·2009·Proceedings of the American Thoracic Society

DOI 10.1513/pats.200904-022rmPMC PMC5820858

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Abstract

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the lungs that usually manifests late in life. Physiologic and immunologic changes that occur in COPD often mimic changes seen in the aging lung. This has led some to characterize COPD as an “accelerated aging phenotype.” At the molecular level, COPD and aging share common mechanisms and are associated with significant dysregulation of the immune systems. Aging and COPD are characterized by increases in proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, which are implicated in aging-related inflammatory diseases and correlate with degree of obstruction in COPD. There is an age-dependent decline in naïve T cells with oligoclonal expansion of CD8+ CD28null T cells from chronic antigenic stimulation. The increase in CD8+ CD28 null T regulatory cells inhibits antigen-specific CD4+ T cell responses, leading to a decline in adaptive immune response. To compensate for the decline in the adaptive immune function there is a paradoxical up-regulation of innate immune system resulting in a proinflammatory state. The dysregulated adaptive immune system with activated innate immune responses seen with aging results in recruitment and retention of neutrophils, macrophages, and CD4+ and CD8+ T cells in the lungs of smokers with COPD. Once the inflammation is triggered, there is a self-perpetuating cascade of inflammation and lung parenchymal damage. This review will focus on how the aging immune system may contribute to COPD development later in life in susceptible individuals.

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Authors: Sharma, G., Hanania, N. A., & Shim, Y. M.
Affiliations: The University of Texas Medical Branch at Galveston (US)
Baylor College of Medicine (US)
University of Virginia (US)
Corresponding author: Sharma, Gulshan
ORCID: Sharma, Gulshan
Shim, Y. Michael
Venue: Proceedings of the American Thoracic Society
Publisher: Oxford University Press (OUP)
Published: 2009-12-01
Volume: 6
Issue: 7
Pages: 573-580
ISSN: 1546-3222 (ISSN-L)
1943-5665
DOI: 10.1513/pats.200904-022rm
PMC: PMC5820858
OpenAlex: W2158912859
Cited by: 105
References: 106
Citations by year: 2026: 5 · 2025: 4 · 2024: 10 · 2023: 4 · 2022: 10 · 2021: 5 · 2020: 2 · 2019: 5 · 2018: 2 · 2017: 7 · 2016: 4 · 2015: 9 · 2014: 7 · 2013: 11 · 2012: 8
FWCI: 0.99
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: Proceedings of the American Thoracic Society (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (K08HL091127)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
Keywords: chronic obstructive pulmonary disease, immunosenescence, inflammatory cytokines, interleukin-6, TNF-α, CD8+CD28- T cells, regulatory T cells, innate immune activation, neutrophil recruitment, macrophages, smoking, lung inflammation
MeSH terms: Aging, Humans, Immunity, Tumor Necrosis Factor-alpha, Interleukin-6, Pulmonary Disease, Chronic Obstructive

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The Aging Immune System and Its Relationship to the Development of Chronic Obstructive Pulmonary Disease

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