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Cord blood vitamin D status: evidence for altered CD4+ naïve and gut-homing T cell accumulation

Published online by Cambridge University Press:  19 April 2013

P. S. Noakes ,
L. J. Michaelis ,
A. P. Williams ,
C. A. Thornton ,
H. Arshad ,
P. C. Calder ,
N. Harvey ,
C. Cooper  and
G. C. Roberts
P. S. Noakes
Affiliation:
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, SO16 6YD
L. J. Michaelis
Affiliation:
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, SO16 6YD
A. P. Williams
Affiliation:
Cancer Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, SO16 6YD
C. A. Thornton
Affiliation:
Institute of Life Science, College of Medicine, Swansea University, Swansea, United Kingdom, SA2 8PP
H. Arshad
Affiliation:
Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, SO16 6YD NIHR Respiratory Biomedical Research Unit, Southampton, United Kingdom, SO16 6YD University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom, SO16 6YD
P. C. Calder
Affiliation:
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, SO16 6YD
N. Harvey
Affiliation:
Southampton Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom, SO16 6YD
C. Cooper
Affiliation:
Southampton Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom, SO16 6YD
G. C. Roberts
Affiliation:
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, SO16 6YD Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, SO16 6YD NIHR Respiratory Biomedical Research Unit, Southampton, United Kingdom, SO16 6YD
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Abstract

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The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), has potent immunomodulatory properties that have prompted its consideration in the prevention of immune-mediated diseases. Recent evidence indicates that the gut is the primary site of tolerance induction where homing receptor switch from α4β7 towards a memory phenotype occurs. However, the role of vitamin D in these processes remains unclear.

The aim of this study is to assess the association of vitamin D status to immune function at birth.

Umbilical cord plasma concentrations of 25(OH)D3 were measured at birth (n=47) and related to a number of cord blood immunological endpoints: (1) enumeration of T, B, NK, iNKT, pDC, mDC cells; (2) skin and gut homing T cells; (3) CD4+CD25+FoxP3+ regulatory T cell numbers; (4) cytokine responses to LPS and mitogen (PHA) and (5) neonatal total IgE levels.

Neonatal 25(OH)D3 was positively associated with the levels of gut homing CD4+CCR9+ T cells (r=0.436, P=0.026). Similar, though not statistically significant, trends were seen for CD8+CCR9+ T cells (r=0.365; P=0.067). Neonatal 25(OH)D3 was not correlated with either skin-homing (CLA+) or CD4+CD25+FoxP3+ regulatory T cell expression. TNF-α and TNF-β release after stimulation with T cell mitogen PHA, were both inversely related to neonatal 25(OH)D3 (TNF-α: r=−0.48, P=0.01; TNF-β: r=−0.43, P=0.02). Furthermore, IL-10 release after LPS stimulation was weakly negatively correlated with 25(OH)D3 (r=−0.35, P=0.07).

These findings suggest that neonatal 25(OH)D3 alters CD4+ gut-homing (CCR9+) and naïve (CCR7+CD45RA+) T cell receptor expression and pro-inflammatory (TNF) cytokine production which could impact on neonatal tolerance mechanisms.

This work is supported by the BUPA Foundation and AAIR Charity. The authors wish to thank staff at the Princess Anne Hospital, Southampton and the Medical Research Council Epidemiology Resource Centre for their invaluable contributions to this study.