Vitamin D3 replacement enhances antigen-specific immunity in older adults

Author:

Chambers Emma S12ORCID,Vukmanovic-Stejic Milica2,Turner Carolin T2,Shih Barbara B3ORCID,Trahair Hugh4,Pollara Gabriele2ORCID,Tsaliki Evdokia2,Rustin Malcolm5,Freeman Tom C3,Mabbott Neil A3,Noursadeghi Mahdad2ORCID,Martineau Adrian R1,Akbar Arne N4

Affiliation:

1. Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK

2. Division of Infection and Immunity, University College London, London, UK

3. The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, UK

4. Division of Medicine, University College London, London, UK

5. Department of Dermatology, Royal Free Hospital, London, UK

Abstract

Summary Introduction Ageing is associated with increased number of infections, decreased vaccine efficacy and increased systemic inflammation termed inflammageing. These changes are reflected by reduced recall responses to varicella zoster virus (VZV) challenge in the skin of older adults. Vitamin D deficiency is more common in the old and has been associated with frailty and increased inflammation. In addition, vitamin D increases immunoregulatory mechanisms and therefore has the potential to inhibit inflammageing. Objectives We investigated the use of vitamin D3 replacement to enhance cutaneous antigen-specific immunity in older adults (≥65 years). Methods Vitamin D insufficient older adults (n = 18) were administered 6400IU of vitamin D3/day orally for 14 weeks. Antigen-specific immunity to VZV was assessed by clinical score assessment of the injection site and transcriptional analysis of skin biopsies collected from challenged injection sites pre- and post-vitamin D3 replacement. Results We showed that older adults had reduced VZV-specific cutaneous immune response and increased non-specific inflammation as compared to young. Increased non-specific inflammation observed in the skin of older adults negatively correlated with vitamin D sufficiency. We showed that vitamin D3 supplementation significantly increased the response to cutaneous VZV antigen challenge in older adults. This enhancement was associated with a reduction in inflammatory monocyte infiltration with a concomitant enhancement of T cell recruitment to the site of antigen challenge in the skin. Conclusion Vitamin D3 replacement can boost antigen-specific immunity in older adults with sub-optimal vitamin D status.

Funder

Medical Research Council

Grand Challenge in Experimental Medicine

Barts Charity Lectureship

Dermatrust

LEO Skin Foundation

Biotechnology and Biological Sciences Research Council

National Institute for Health Research University College London Hospitals Biomedical Research Centre

Publisher

Oxford University Press (OUP)

Subject

General Medicine

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