Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Age-related alterations in blood and colonic dendritic cell properties

Rakesh Vora, David Bernardo, Lydia Durant, Durga Reddi, Ailsa L. Hart, John M. E. Fell, Hafid O. Al-Hassi and Stella C. Knight _

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Oncotarget. 2016; 7:11913-11922. https://doi.org/10.18632/oncotarget.7799

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Abstract

Rakesh Vora1,2,3,*, David Bernardo1,4,*, Lydia Durant1, Durga Reddi1, Ailsa L. Hart1,2, John M. E. Fell1,3, Hafid O. Al-Hassi1 and Stella C. Knight1

1 Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark’s Campus, Harrow, UK

2 London North West Healthcare NHS Trust, St. Mark’s Campus, Harrow, UK

3 Chelsea and Westminster Hospital NHS Foundation Trust, London, UK

4 Gastroenterology Unit, Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa (IIS-IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain

* These authors have contributed equally to this work

Correspondence to:

Stella C. Knight, email:

Keywords: mDC, pDC, children, aging, cytokines, BDCA-2, Gerotarget

Received: September 14, 2015 Accepted: January 30, 2016 Published: March 01, 2016

Abstract

Background: Dendritic cells (DC) determine initiation, type and location of immune responses and, in adults, show decreased Toll-like receptors and some increased cytokine levels on ageing. Few studies in children have characterised DC or explored DC-related mechanisms producing age-related immune changes.

Results: The pDC marker BDCA2 (but not CD123) was absent in pre-pubertal children and numbers of pDC decreased with age. Blood and colonic DC were more mature and activated in adults. Decrease in pDC numbers correlated with reduced GM-CSF levels with aging, but increasing IL-4 and IL-8 levels correlated with a more activated DC profile in blood. CXCL16 levels decreased with age.

Methods: Blood and colonic DC phenotypes were determined in healthy adults and children by flow cytometry and correlated with aging. Blood DC were divided into plasmacytoid (pDC) and myeloid (mDC) while only mDC were identified in colon. Serum cytokine levels were determined by multiplex cytokine assays and correlated with DC properties.

Conclusions: In children, lack of BDCA2, a receptor mediating antigen capture and inhibiting interferon induction, may be immunologically beneficial during immune development. Conversely, reduced pDC numbers, probably secondary to decreasing GM-CSF and increasing cytokine-induced maturation of DC are likely to determine deteriorating immunity with ageing.


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