Dendritic cells from aged subjects contribute to chronic airway inflammation by activating bronchial epithelial cells under steady state.
The mechanisms underlying the increased susceptibility of the elderly to respiratory infections are not well understood. The crosstalk between the dendritic cells (DCs) and epithelial cells is essential in maintaining tolerance as well as in generating immunity in the respiratory mucosa. DCs from aged subjects display an enhanced basal level of activation, which can affect the function of epithelial cells. Our results suggest that this is indeed the scenario as exposure of primary bronchial epithelial cells (PBECs) to supernatants from unstimulated DCs of aged subjects resulted in activation of PBECs. The expression of CCL20, CCL26, CXCL10, mucin, and CD54 was significantly increased in the PBECs exposed to aged DC supernatants, but not to young DC supernatants. Furthermore, aged DC supernatants also enhanced the permeability of the PBEC barrier. We also found that DCs from aged subjects spontaneously secreted increased levels of pro-inflammatory mediators, interleukin-6, tumor necrosis factor (TNF)-α, and metalloproteinase A disintegrin family of metalloproteinase 10, which can affect the functions of PBECs. Finally, we demonstrated that TNF-α, present in the supernatant of DCs from aged subjects, was the primary pro-inflammatory mediator that affected PBEC functions. Thus, age-associated alterations in DC-epithelial interactions contribute to chronic airway inflammation in the elderly, increasing their susceptibility to respiratory diseases.
Division of Basic and Clinical Immunology, Department of Medicine, University of California-Irvine, Irvine, California, USA.
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Prakash
Division of Basic and Clinical Immunology, Department of Medicine, University of California-Irvine, Irvine, California, USA.
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Agrawal
Cellular and Molecular Immunology Laboratory, Gavin Herbert Eye Institute, University of California-Irvine, Irvine, California, USA.
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Vahed
Division of Basic and Clinical Immunology, Department of Medicine, University of California-Irvine, Irvine, California, USA.
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Ngyuen
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BenMohamed
Cellular and Molecular Immunology Laboratory, Gavin Herbert Eye Institute, University of California-Irvine, Irvine, California, USA.
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BenMohamad
Division of Basic and Clinical Immunology, Department of Medicine, University of California-Irvine, Irvine, California, USA.
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Gupta
Division of Basic and Clinical Immunology, Department of Medicine, University of California-Irvine, Irvine, California, USA.
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Agrawal
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology* / Q000473:pathology; D001980:Bronchi / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D002908:Chronic Disease; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020545:Respiratory Mucosa / Q000276:immunology* / Q000473:pathology; D012140:Respiratory Tract Diseases / Q000276:immunology* / Q000473:pathology
D018836:Inflammation Mediators