Abundant laboratory findings show the important role vitamin D has in the innate and adaptive immune system. In human beings, observational studies have associated vitamin D deficiency with an increased risk for different inflammatory, infectious, and autoimmune diseases. With regard to chronic obstructive pulmonary disease (COPD), conflicting data have been reported. Most epidemiological studies have been restricted by their design, and larger longitudinal studies of population-based samples and of cohorts with COPD are warranted. An alternative explanation for the discordant results in COPD might be related to the complexity of the intracellular vitamin D signalling pathway, which is not shown in systemic levels of the precursor 25-hydroxyvitamin D. For COPD in particular, we speculate that local downregulation of vitamin D signalling from and beyond the receptor might clarify why pro-inflammatory processes in the airways are not or are insufficiently countered by vitamin D-dependent control mechanisms. In a disease already characterised by glucocorticoid resistance, the potential activation and reactivation of an intrinsic comprehensive system of immune control should attract more attention to design appropriate interventions with promising therapeutic potential.
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