Once matured, DCs direct naive T cells towards either a Th1 or Th2 phenotype, based on the type of stimulus inducing maturation and cues from the external environment. For example, DCs matured in the presence

of prostaglandin E2 (PGE2) promote Th2 responses [4]. Furthermore, DC expression of CD86+ has been shown to be elevated in Th2-skewed respiratory diseases such as asthma and allergic rhinitis [5,6]. Macrophages represent another class of APC that regulate inflammation. In response to cytokines and microbial products, macrophages produce proinflammatory and anti-inflammatory mediators [7,8]. Elevated numbers of macrophages GDC-0199 are observed in asthma [9], yet it is unclear if they are elevated Ganetespib manufacturer systemically in sinusitis. Like DCs, their ability to regulate downstream immune responses suggests that they may contribute to the inflammatory response in

sinusitis. Vitamin D3 (VD3) is an immunomodulatory steroid hormone that regulates DC, monocyte, macrophage and T cell functions. VD3 plays an important role as an immune regulator through its ability to block monocyte to DC differentiation and maturation, thereby diminishing DCs ability to stimulate T cell Th1/Th2 differentiation [10]. Several studies have also shown that exposure of DCs to VD3 re-programs them to support a tolerogenic phenotype [11–13]. In macrophages, VD3 has been shown to exert an opposite effect, promoting monocyte to macrophage differentiation and proliferation [14]. Therefore, VD3 may play an important role in inflammatory diseases such as CRS. Increasing evidence suggests that VD3 plays an important role in respiratory health. For example, in a study of 6–14-year-old

children with asthma, 28% were determined to have severe VD3 deficiencies. Furthermore, increased VD3 levels were associated with reduced likelihood for being hospitalized and reduced use of anti-inflammatory medications [15]. In steroid-resistant asthmatics it has been shown Niclosamide that VD3 administration can down-regulate Th2 skewing [16]. Data from the Third National Health and Nutrition Examination Survey (NHANES III) showed that VD3 levels are associated inversely with the occurrence of upper respiratory tract infections, and this association was even stronger in those with asthma [17]. In the upper airway, two reports have examined the role of VD3 in allergic rhinitis. Using data from the NHANES III, Wjst and Hypponen found that the prevalence of allergic rhinitis increased across quartile groups of VD3 serum levels [18]. Pinto et al. observed that African Americans with allergic rhinitis have lower VD3 levels than race- and age-matched controls, suggesting that VD3 has a potential role in upper respiratory disease in African Americans [19].