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Background: Low vitamin D levels have been associated with allergic diseases. Vitamin D has potent immunomodulatory properties, but the mechanisms remain unclear. We have investigated the effect of oral vitamin D supplementation on circulating immune cell phenotypes in infants. Method: A double‐blinded randomised controlled trial was conducted to investigate the effect of oral vitamin D supplementation (400 IU/d) on eczema and immune development. A subset of 78 infants was included in this analysis. Phenotypic analysis of immune cell subsets was performed using flow cytometry. Results: Vitamin D supplementation resulted in median 25(OH)D levels of 80.5 vs 59.5 nmol/L in the placebo group at 3 months of age (P =.002) and 87.5 vs 77 nmol/L at 6 months of age (P =.08). We observed significant changes in immune cell composition from birth (cord blood) to 6 months of age. Vitamin D supplementation did not impact these changes, nor did immune cell composition correlate with plasma 25(OH)D levels. Through exploratory analysis, we identified possible associations with eczema development and increased abundance of naïve CD4‐ T cells at birth, as well as associations with basophils, iNKT and central memory CD4+ T cells, and altered expression patterns of IgE receptor (FcεR1) on monocytes and dendritic cells with eczema at 6 months. Conclusions: Vitamin D supplementation in infants who were vitamin D sufficient at birth did not affect developmental changes in immune cells during the first 6 months of life. However, immune cell profiles at birth and at 6 months of age were associated with early life eczema. [ABSTRACT FROM AUTHOR]

Background: Antigen‐specific IgE binds the Fcε receptor I (FcεRI) expressed on several types of immune cells, including dendritic cells (DCs). Activation of FcεRI on DCs in atopics has been shown to modulate immune responses that potentially contribute to asthma development. However, the extent to which DC subsets differ in FcεRI expression between atopic children with or without asthma is currently not clear. This study aimed to analyse the expression of FcεRI on peripheral blood mononuclear cells (PBMCs) from atopic children with and without asthma, and non‐atopic/non‐asthmatic age‐matched healthy controls. Methods: We performed multiparameter flow cytometry on PBMC from 391 children across three community cohorts and one clinical cohort based in Western Australia. Results: We confirmed expression of FcεRI on basophils, monocytes, plasmacytoid and conventional DCs, with higher proportions of all cell populations expressing FcεRI in atopic compared to non‐atopic children. Further, we observed that levels of FcεRI expression were elevated across plasmacytoid and conventional DC as well as basophils in atopic asthmatic compared to atopic non‐asthmatic children also after adjusting for serum IgE levels. Conclusion: Our data suggest that the expression pattern of FcεRI on DC and basophils differentiates asthmatic from non‐asthmatic atopic children. Given the significant immune modulatory effects observed as a consequence of FcεRI expression, this altered expression pattern is likely to contribute to asthma pathology in children. [ABSTRACT FROM AUTHOR]

To cite this article: Lisciandro JG, Prescott SL, Nadal-Sims MG, Devitt CJ, Pomat W, Siba PM., Holt PG, Strickland D, van den Biggelaar AHJ. Comparison of neonatal T regulatory cell function in Papua New Guinean and Australian newborns. Pediatr Allergy Immunol 2011: Doi: 10.1111/j.1399-3038.2011.01242.x. Abstract Background: Environmental changes, including declining microbial exposure, have been linked with the rising incidence of allergic and autoimmune diseases in 'western' populations. This potentially occurs by altering early development of immuno-regulatory pathways including T regulatory cells (Treg). There is now increasing evidence that such conditioning begins in utero. Methods: We compared neonatal Treg from children born under typical western conditions (Australia, AUS) with those of neonates born under more traditional conditions of high microbial burden (Papua New Guinea, PNG). Results: The frequency of neonatal Treg, defined as CD4+ Foxp3+ CD127− CD25+/high was found to be higher in the cord blood of AUS compared to PNG newborns. However, cord Treg suppressive function in a small subset of children was qualitatively similar between PNG and AUS newborns in both a Treg depletion assay and a Treg supplementation assay. Conclusions: These findings do not support the hypothesis that living in a 'western' versus more traditional environment leads to poor induction or suppressive function of neonatal Treg. However, environmentally-induced immuno-regulation may potentially occur via alternative mechanisms in PNG newborns that should now be investigated further. [ABSTRACT FROM AUTHOR]