Alterations in Gene Array Patterns in Dendritic Cells from Aged Humans

Mediators of Inflammation

et al. 2014

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Chlamydophila pneumoniae (CPn) is a common respiratory pathogen that causes a chronic and persistent airway infection. The elderly display an increased susceptibility and severity to this infection. However, the underlying mechanisms are not well understood. Dendritic cells (DCs) are the initiators and regulators of immune responses. Therefore, we investigated the role of DCs in the age-associated increased CPn infection in vitro in humans. Though the expression of activation markers was comparable between the two age groups, DCs from aged subjects secreted enhanced levels of proinflammatory mediators such as TNF-α and CXCL-10 in response to CPn. In contrast, the secretion of IL-10 and innate interferons, IFN-α and IFN-λ, was severely impaired in DCs from aged donors. The increased activation of DCs from aged subjects to CPn also resulted in enhanced proliferation of CD4 and CD8 T cells in a DC-T coculture. Furthermore, T cells primed with CPn-stimulated DCs from aged subjects secreted increased levels of IFN-γ and reduced levels of IL-10 compared to DCs obtained from young subjects. In summary, DCs from the elderly displayed enhanced inflammatory response to CPn which may result in airway remodeling and increase the susceptibility of the elderly to respiratory diseases such as asthma.

Section: Discussionsupporting

confidence: 91%

Dendritic Cells from Aged Subjects Display Enhanced Inflammatory Responses toChlamydophila pneumoniae

Prakash

Mediators of Inflammation

et al. 2014

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“…Ageing has a significant impact on DC functions [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Several reports suggest that phagocytosis, migration, and cytokine secretion are impaired in DCs isolated from aged individuals (60–90 years of age) compared to DCs from young individuals (20–40 years of age) [ 25 ].…”

Section: Age-associated Deterioration And/or Dysregulation Of Humamentioning

confidence: 99%

Dendritic Cell-Airway Epithelial Cell Cross-Talk Changes with Age and Contributes to Chronic Lung Inflammatory Diseases in the Elderly

2017

IJMS

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Age-associated dysregulated immune and inflammatory responses are one of the major factors responsible for the prevalence of chronic respiratory diseases in the older population. Pulmonary dendritic cells (DCs) are present below the airway epithelial cells (AECs) and are critical in initiating effective immune responses to harmful pathogens while maintaining tolerance against harmless antigens. The interaction between DCs and AECs plays a crucial role in lung immunity at homeostasis and during infections. The functions of both DCs and AECs are impacted with age. The present report reviews how the potential crosstalk between pulmonary DCs and AECs is dysregulated in the elderly impairing the capacity to maintain tolerance at the respiratory surfaces, which results in severe and chronic respiratory inflammatory diseases. We also discuss how such DC-AECs crosstalk will provide insight into the mechanisms underlying the increased susceptibility of the elderly to pulmonary inflammatory diseases.

“…CD141 was chosen because CD141 + DCs are reported to be the human homolog of CD103 + DCs [ 25 ]. GARP was chosen because it was found to be significantly downregulated in DCs from aged compared to DCs from young subjects in our gene array data [ 26 ]. GARP expression has previously been reported on platelets and T regulatory cells where it plays an important role in tethering latent TGF-β on the surface [ 27 , 28 ].…”

Section: Resultsmentioning

confidence: 99%

Retinoic acid treated human dendritic cells induce T regulatory cells via the expression of CD141 and GARP which is impaired with age

Ganguly

Tran

et al. 2016

Aging

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Aged subjects display increased susceptibility to mucosal diseases. Retinoic Acid (RA) plays a major role in inducing tolerance in the mucosa. RA acts on Dendritic cells (DCs) to induce mucosal tolerance. Here we compared the response of DCs from aged and young individuals to RA with a view to understand the role of DCs in age-associated increased susceptibility to mucosal diseases. Our investigations revealed that compared to young DCs, RA stimulated DCs from aged subjects are defective in inducing IL-10 and T regulatory cells. Examinations of the underlying mechanisms indicated that RA exposure led to the upregulation of CD141 and GARP on DCs which rendered the DCs tolerogenic. CD141hi, GARP+ DCs displayed enhanced capacity to induce T regulatory cells compared to CD141lo and GARP− DCs. Unlike RA stimulated DCs from young, DCs from aged subjects exhibited diminished upregulation of both CD141 and GARP. The percentage of DCs expressing CD141 and GARP on RA treatment was significantly reduced in DCs from aged individuals. Furthermore, the remaining CD141hi, GARP+ DCs from aged individuals were also deficient in inducing T regs. In summary, reduced response of aged DCs to RA enhances mucosal inflammation in the elderly, increasing their susceptibility to mucosal diseases.