1α,25-Dihydroxyvitamin D3 Supplementation during Pregnancy Is Associated with Allergic Rhinitis in the Offspring by Modulating Immunity
Authors: Xiaoyang Yuan
Zhen Zhou
Yong Li
Junbo Xia
Haifeng Ni
Liqing Zhang
Bo Jiang
Journal: Journal of Immunology Research (2021)
Discipline: IMMUNOLOGY
Keywords: Maternal supplementation; 1α,25-dihydroxyvitamin D3; immune dysregulation; offspring; allergic rhinitis
Affiliations: Department of Otolaryngology, Tongxiang First People’s Hospital, Tongxiang, Zhejiang 314500, China, Department of Otolaryngology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China

Abstract:  Background: Maternal supplementation with 1α,25-dihydroxyvitamin D3 (VD3) has immunologic effects on the developing fetus through multiple pathways. This study was aimed at investigating the effects of VD3 supplementation on immune dysregulation in the offspring during allergic rhinitis. Methods: Different doses of VD3 as well as control were given to pregnant female mice. Ovalbumin (OVA) challenge and aluminum hydroxide gel in sterile saline were used to induce allergic rhinitis in offspring mice. Nasal lavage fluids (NLF) were collected, and eosinophils were counted in NLF 24 hours after the OVA challenge. Th1, Th2, Th17, and Treg subtype-relevant cytokines, including IFN-γ, IL-4, IL-10, IL-17, TGF-β, and OVA-IgE levels from the blood and NLF of offspring mice, were detected by the enzyme-linked immunosorbent assay (ELISA) method. The Treg subtype was analyzed by flow cytometry. Treg cells were purified from offspring and were adoptively transferred to OVA-sensitized allogenic offspring mice. The outcomes were assessed in allogenic offspring. Results: Our data showed that VD3 supplementation significantly decreased the number of eosinophils, basophils, and lymphocytes in the peripheral blood and NLF. The proportion of CD4+CD25+FoxP3+Tregs had a positive correlation with VD3 in a dose-dependent manner. The levels of serum IgE, IL-4, and IL-17 were decreased while the expressions of IFN-γ, IL-10, and TGF-β were significantly enhanced in VD3 supplementation groups. Adoptive transfer CD4+CD25+FoxP3+Tregs of VD3 supplementation groups promoted Th1 and suppressed Th2 responses in the offspring during allergic rhinitis. Conclusion: Our findings indicated that low dose VD3 supply in pregnant mice's diet suppressed Th2 and Th17 responses in allergic rhinitis by elevating the Th1 subtype and the proportion of CD4+CD25+FoxP3+Tregs in offspring. It suggested that low dose VD3 supply may have the potential to act as a new therapeutic strategy for allergic rhinitis. 

Retracted: No

PubPeer comments:
 According to the methods a total of 25 eight-week-old female BALB c mice were purchased from the Animal Resources Centre (Nanjing, China)... The female mice were allowed to mate with males at a 2 : 1 ratio, and mating was confirmed by observing the vaginal smear. Where did the male mice come from? I wonder also what the authors measured in Fig 1 as Abcam (Cambridge, MA, USA) does not sell any mouse  VD3 (1u03b1,25-Dihydroxyvitamin D3) calcitriol ELISA but a 25-OH-D3 Assay. Fig 2 seems to have a 10fold higher white blood cell count [than expected] . Why? I have to confess that I have also never seen such a beautiful dose dependent linear increase in every assay. ![file] Could we see also clear FACS images? And why are those 2 plots basically identical? ![file] And yes - I would have expected results like those of reference 24 . Maybe the authors could explain why their results are so much different? ,