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The concept that extra-skeletal functions of vitamin D impact on human health have taken place since quite ago. Among all, the beneficial effects of vitamin D on immune regulation, skeletal muscle function, and metabolism are undeniable. Adequate vitamin D levels maintain the immune system and skeletal muscle metabolism integrity, promoting whole-body homeostasis; hypovitaminosis D associates with the important decline of both tissues and promotes chronic inflammation, which is recognized to underlie several disease developments. Growing evidence shows that the immune system and skeletal muscle reciprocally dialogue, modulating each other’s function. Within this crosstalk, vitamin D seems able to integrate and converge some biomolecular signaling towards anti-inflammatory protective effects. Thus, vitamin D regulation appears even more critical at the immune system-muscle signaling intersection, rather than at the single tissue level, opening to wider/newer opportunities in clinical applications to improve health. This paper aims to focus on the immune system-skeletal muscle interplay as a multifaceted target for vitamin D in health and disease after recalling the main regulatory functions of vitamin D on those systems, separately. Some myokines, particularly relevant within the immune system/skeletal muscle/vitamin D networking, are discussed. Since vitamin D supplementation potentially offers the opportunity to maintain health, comments on this issue, still under debate, are included.

Vitamin D Merging into Immune System-Skeletal Muscle Network: Effects on Human Health