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.

These studies identify that children with CRSwNP or AFRS are vitamin D(3) deficient, which may be linked to increased dendritic cell infiltrate. These results suggest a role for vitamin D(3) as a key player in the immunopathology of pediatric CRSwNP.