The authors found that the CD4+CD25hiFoxP3+ Tregs cells were significantly increased, concomitant with increased endogenous synthesis of 1, 25-dihydroxyvitamin D3.[41] Several lines of research have demonstrated that VDR activation promotes Th cell polarization by inhibiting Th1 and by augmenting Th2 cell development, thus inhibiting IFN-gamma and up-regulating IL-4, IL-5,

and IL-10 production.[42] The VD-induced effects were largely mediated via IL-4, as IL-4 neutralization almost completely abrogated the observed augmented Th2 RAD001 cell development after D3 treatment. Furthermore, increased expression of the Th2-specific transcription factors GATA-3 and c-maf correlated with increased production of Th2 cytokines after VD treatment. In addition, allergic asthma is tightly associated with Th2 cells. VDR knockout mice, however, failed to develop experimentally induced allergic asthma, suggesting an important role for VD signaling in the click here generation of Th2-driven inflammation.[43] On the other hand, 1,25-dihydroxyvitamin D can suppress Th2 skewed immune responses via naive Tregs.[44] Indeed, administration of 1,25-dihydroxyvitamin D significantly suppressed ovalbumin (OVA)-induced allergy through reduction of serum OVA-specific IgE levels, airway eosinophilia, and Th2-related cytokines.[45] VD deficiency is frequently found in chronic

liver diseases.[46] Active VD can suppress hepatic stellate cell activation in vitro and hepatic toxin-induced cirrhosis in a rat model.[47] However, it is still ambiguous as to what level is regarded as VD insufficiency or deficiency apart from its classic definition for calcium adsorption/deposition.

Neither the VD standard for health liver function is defined, nor the threshold for chronic liver diseases is known. A working standard has been generally adapted from the Endocrine Society, which defined that 32 ng/mL should be used as the threshold for 25(OH)D sufficiency in patients with various disease conditions.[48] Non-alcoholic MCE fatty liver disease (NAFLD) is characterized by hepatic steatosis in patients who do not exhibit alcohol abuse or other known liver diseases. Non-alcoholic steatohepatitis (NASH) is a progressive form of NAFLD characterized by both hepatic inflammation and lipid excessiveness. NAFLD affects about 20–30% of the adult population and 8% of adolescents in many countries.[49] NAFLD is tightly associated with obesity, metabolic syndrome, insulin resistance, and type-II diabetes mellitus, which are related to VD deficiency or insufficiency.[50] In particular, serum 25-hydroxyvitamin D levels have been found to be inversely related to body mass index and body fat content, hypertension, insulin resistance, and diabetes mellitus.[51, 52] Importantly, the results from a clinical trial on obese adolescents showed that body fat content is significantly associated with VD deficiency or insufficiency.