Impact of dietary vitamin D on immunoregulation and disease pathology in lupus-prone NZB/W F1 mice.

Frontiers in immunology 2022 Nov 24

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Vitamin D (VD) deficiency is a highly prevalent worldwide phenomenon and is extensively discussed as a risk factor for the development of systemic lupus erythematosus (SLE) and other immune-mediated diseases. In addition, it is now appreciated that VD possesses multiple immunomodulatory effects. This study aims to explore the impact of dietary VD intake on lupus manifestation and pathology in lupus-prone NZB/W F1 mice and identify the underlying immunological mechanisms modulated by VD. Here, we show that low VD intake accelerates lupus progression, reflected in reduced overall survival and an earlier onset of proteinuria, as well higher concentrations of anti-double-stranded DNA autoantibodies. This unfavorable effect gained statistical significance with additional low maternal VD intake during the prenatal period. Among examined immunological effects, we found that low VD intake consistently hampered the adoption of a regulatory phenotype in lymphocytes, significantly reducing both IL-10-expressing and regulatory CD4+ T cells. This goes along with a mildly decreased frequency of IL-10-expressing B cells. We did not observe consistent effects on the phenotype and function of innate immune cells, including cytokine production, costimulatory molecule expression, and phagocytic capacity. Hence, our study reveals that low VD intake promotes lupus pathology, likely via the deviation of adaptive immunity, and suggests that the correction of VD deficiency might not only exert beneficial functions by preventing osteoporosis but also serve as an important module in prophylaxis and as an add-on in the treatment of lupus and possibly other immune-mediated diseases. Further research is required to determine the most appropriate dosage, as too-high VD serum levels may also induce adverse effects, possibly also on lupus pathology. Copyright © 2022 Kraemer, Schäfer, Sprenger, Sehnert, Williams, Luo, Riechert, Al-Kayyal, Dumortier, Fauny, Winter, Heim, Hofmann, Herrmann, Heine, Voll and Chevalier.

Citation

Antoine N Kraemer, Anna-Lena Schäfer, Dalina T L Sprenger, Bettina Sehnert, Johanna P Williams, Aileen Luo, Laura Riechert, Qusai Al-Kayyal, Hélène Dumortier, Jean-Daniel Fauny, Zoltan Winter, Kathrin Heim, Maike Hofmann, Martin Herrmann, Guido Heine, Reinhard E Voll, Nina Chevalier. Impact of dietary vitamin D on immunoregulation and disease pathology in lupus-prone NZB/W F1 mice. Frontiers in immunology. 2022 Nov 24;13:933191