Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local 25 (OH)D3 metabolism

Jennifer K. Mulligan, Whitney N. Pasquini, William Wise Crosby Carroll, Tucker Williamson, Nicholas Reaves, Kunal J. Patel, Elliott Mappus, Rodney J. Schlosser, Carl Atkinson

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Rationale: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be vitamin D3 (VD3) deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic rhinosinusitis (Af-CRS). Methods: Balb/c mice were fed control or VD3 deficient diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week later given Af intranasally every three days for four weeks while being maintained on control or VD3 deficient diet. Airway function, sinonasal immune cell infiltrate and sinonasal VD3 metabolism profiles were then examined. Results: Mice with VD3 deficiency had increased Penh and sRaw values as compared to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1α-hydroxylase and the active VD3 metabolite, 1,25(OH)2D3. Differential analysis of nasal lavage samples showed that VD3 deficiency alone and in combination with Af-CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3 deficiency exacerbated increases in monocyte-derived dendritic cell (DC) associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af-CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a modifying or exacerbating impact on nasal lavage levels of IFN-γ, IL-6, IL-10 and TNF-α, but had no impact on IL-17A. Conclusions: VD3 deficiency causes changes in sinonasal immunity, which in many ways mirrors the changes observed in Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3 deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism causing reductions in local levels of the active VD3 metabolite, 1,25(OH)2D3, even with adequate circulating levels.

Original languageEnglish (US)
Article numbere0186374
JournalPLoS One
Volume12
Issue number10
DOIs
StatePublished - Oct 1 2017
Externally publishedYes

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Avitaminosis
cholecalciferol
Cholecalciferol
Metabolism
Aspergillus fumigatus
inflammation
Aspergillus
Inflammation
metabolism
mice
Nasal Lavage
Nutrition
Metabolites
metabolites
Diet
Nasal Polyps

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Mulligan, J. K., Pasquini, W. N., Carroll, W. W. C., Williamson, T., Reaves, N., Patel, K. J., ... Atkinson, C. (2017). Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local 25 (OH)D3 metabolism. PLoS One, 12(10), [e0186374]. https://doi.org/10.1371/journal.pone.0186374

Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local 25 (OH)D3 metabolism. / Mulligan, Jennifer K.; Pasquini, Whitney N.; Carroll, William Wise Crosby; Williamson, Tucker; Reaves, Nicholas; Patel, Kunal J.; Mappus, Elliott; Schlosser, Rodney J.; Atkinson, Carl.

In: PLoS One, Vol. 12, No. 10, e0186374, 01.10.2017.

Research output: Contribution to journalArticle

Mulligan, JK, Pasquini, WN, Carroll, WWC, Williamson, T, Reaves, N, Patel, KJ, Mappus, E, Schlosser, RJ & Atkinson, C 2017, 'Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local 25 (OH)D3 metabolism', PLoS One, vol. 12, no. 10, e0186374. https://doi.org/10.1371/journal.pone.0186374
Mulligan, Jennifer K. ; Pasquini, Whitney N. ; Carroll, William Wise Crosby ; Williamson, Tucker ; Reaves, Nicholas ; Patel, Kunal J. ; Mappus, Elliott ; Schlosser, Rodney J. ; Atkinson, Carl. / Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local 25 (OH)D3 metabolism. In: PLoS One. 2017 ; Vol. 12, No. 10.
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abstract = "Rationale: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be vitamin D3 (VD3) deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic rhinosinusitis (Af-CRS). Methods: Balb/c mice were fed control or VD3 deficient diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week later given Af intranasally every three days for four weeks while being maintained on control or VD3 deficient diet. Airway function, sinonasal immune cell infiltrate and sinonasal VD3 metabolism profiles were then examined. Results: Mice with VD3 deficiency had increased Penh and sRaw values as compared to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1α-hydroxylase and the active VD3 metabolite, 1,25(OH)2D3. Differential analysis of nasal lavage samples showed that VD3 deficiency alone and in combination with Af-CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3 deficiency exacerbated increases in monocyte-derived dendritic cell (DC) associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af-CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a modifying or exacerbating impact on nasal lavage levels of IFN-γ, IL-6, IL-10 and TNF-α, but had no impact on IL-17A. Conclusions: VD3 deficiency causes changes in sinonasal immunity, which in many ways mirrors the changes observed in Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3 deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism causing reductions in local levels of the active VD3 metabolite, 1,25(OH)2D3, even with adequate circulating levels.",
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AU - Reaves, Nicholas

AU - Patel, Kunal J.

AU - Mappus, Elliott

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N2 - Rationale: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be vitamin D3 (VD3) deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic rhinosinusitis (Af-CRS). Methods: Balb/c mice were fed control or VD3 deficient diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week later given Af intranasally every three days for four weeks while being maintained on control or VD3 deficient diet. Airway function, sinonasal immune cell infiltrate and sinonasal VD3 metabolism profiles were then examined. Results: Mice with VD3 deficiency had increased Penh and sRaw values as compared to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1α-hydroxylase and the active VD3 metabolite, 1,25(OH)2D3. Differential analysis of nasal lavage samples showed that VD3 deficiency alone and in combination with Af-CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3 deficiency exacerbated increases in monocyte-derived dendritic cell (DC) associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af-CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a modifying or exacerbating impact on nasal lavage levels of IFN-γ, IL-6, IL-10 and TNF-α, but had no impact on IL-17A. Conclusions: VD3 deficiency causes changes in sinonasal immunity, which in many ways mirrors the changes observed in Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3 deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism causing reductions in local levels of the active VD3 metabolite, 1,25(OH)2D3, even with adequate circulating levels.

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