Vitamin D3 correlates inversely with systemic dendritic cell numbers and bone erosion in chronic rhinosinusitis with nasal polyps and allergic fungal rhinosinusitis

Abstract

SummaryVitamin D3 (VD3) is a steroid hormone that regulates bone health and numerous aspects of immune function and may play a role in respiratory health. We hypothesized that T helper type 2 (Th2) disorders, chronic rhinosinusitis with nasal polyps (CRSwNP) and allergic fungal rhinosinusitis (AFRS) would have VD3 deficiencies, resulting in increased mature dendritic cells (DCs) and bone erosion. We conducted a retrospective study examining VD3 levels in patients with AFRS (n = 14), CRSwNP (n = 9), chronic rhinosinusitis without nasal polyps (CRSsNP) (n = 20) and cerebrospinal fluid leak repair (non-diseased controls) (n = 14) at time of surgery. Circulating immune cell levels were determined by immunostaining and flow cytometric analysis. Plasma VD3 and immune regulatory factors (granulocyte-macrophage colony-stimulating factor and prostaglandin E2) were measured by enzyme-linked immunosorbent assay. It was observed that CRSwNP and AFRS demonstrated increased circulating DCs, while chronic rhinosinusitis without nasal polyps displayed increased circulating macrophages. CRSwNP and AFRS were to found to have insufficient levels of VD3 which correlated inversely with circulating numbers of mature DCs, DC regulatory factors and bone erosion. CRSsNP displayed no change in circulating DC numbers or VD3 status compared to control, but did display increased numbers of circulating macrophages that was independent of VD3 status. Lastly, VD3 deficiency was associated with more severe bone erosion. Taken together, these results suggest support a role for VD3 as a key player in the immunopathology of CRSwNP and AFRS.

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

“…A series of case-control studies have consistently found no significant difference in circulating or sinonasal tissue 25VD 3 levels of CRSsNP patients vs controls in both adult and pediatric patients. [425][426][427] Pinto et al 428 found that African Americans with severe CRS-diagnosed by consensus on symptoms, nasal endoscopy, and CT scan results-had significantly lower serum 25VD 3 levels than both Caucasian patients and race/sex matched controls. However, the composition of CRS patients was not defined and may have included a heterogeneous group of CRSwNP and CRSsNP.…”

“…In contrast to CRSwNP, there does not appear to be any relationship between systemic or local dendritic cells and VD 3 in adult or pediatric CRSsNP patients. 425,426 Others have examined osteoblasts and VD 3 in CRS. Sugimoto et al 431 showed that ethmoid bone osteoblasts in CRS produced greatest mineralization and secreted greatest osteocalcin (a marker of bone mineralization) when incubated in a VD 3 /vitamin K culture solution.…”

“…This work may partly explain the inverse correlation between 25VD 3 levels and bone erosion noted in some clinical studies. 426,432,433 Two statements can be made about VD 3 in CRSsNP:…”

New Insights into Upper Airway Innate Immunity

“…57 Recent research has focused on the relationship between vitamin D and the regulation of the LL-37 gene in sinonasal epithelial cells 58,59 and the implications of this in innate immunity, 60 CRS, and allergic rhinitis. [61][62][63][64] Reactive oxygen and nitrogen species generated by the sinonasal epithelium are also thought to play an essential role in upper airway innate immunity. NO in the upper airway originates predominantly from the paranasal sinuses, particularly the maxillary sinuses.…”

Deficiency of Vitamin D in Allergic Rhinitis: A Possible Factor in Multifactorial Disease

“…Vitamin D has immunomodulatory steroid hormone properties and directly affects dendritic cell, monocyte, macrophage, B cell, and T cell functions 21,22 ( Fig. 1: vitamin D effects on immune system).…”