Vitamin D3 administration to MS patients leads to increased serum levels of latency activated peptide (LAP) of TGF-beta

1α,25‐dihydroxyvitamin D3 acts via transforming growth factor‐β to up‐regulate expression of immunosuppressive CD73 on human CD4+ Foxp3– T cells

“…1,25(OH) 2 D3 increased expression of LAP (component of latent TGF‐ β ), GARP (latent TGF‐ β receptor) and GP96 (latent TGF‐ β chaperone), which together result in cells that have an enhanced capacity to both generate and present latent TGF‐ β . These data are in line with a study in patients with multiple sclerosis in whom vitamin D supplementation resulted in increased levels of LAP in the serum relative to those in the placebo group . Although a whole host of molecules and environmental conditions such as heat and extreme pH have been implicated in activating TGF‐ β by cleaving LAP, α v integrins, neuropilin‐1 and thrombospondin‐1 are the primary mediators within the immune cell compartment; here expression of each of these molecules, at least at the mRNA level, was shown to be higher in 1,25(OH) 2 D3‐treated cells, which most likely contributed to the enhanced TGF‐ β bioactivity observed.…”

“…These data are in line with a study in patients with multiple sclerosis in whom vitamin D supplementation resulted in increased levels of LAP in the serum relative to those in the placebo group. 33 Although a whole host of molecules and environmental conditions such as heat and extreme pH have been implicated in activating TGF-b by cleaving LAP, a v integrins, neuropilin-1 and thrombospondin-1 are the primary mediators within the immune cell compartment; 18 here expression of each of these molecules, at least at the mRNA level, was shown to be higher in 1,25 (OH) 2 D3-treated cells, which most likely contributed to the enhanced TGF-b bioactivity observed. In addition to its anti-inflammatory role, TGF-b is involved in tissue remodelling and therefore can have potentially negative consequences in diseases such as asthma.…”

The impact of vitamin D3 intake on inflammatory markers in multiple sclerosis patients and their first-degree relatives

“…Ahangar-Parvin et al [13] illustrated that the expression of TGF-β up-regulates in EAE mice after vitamin D 3 supplementation. Interestingly enough, a similar finding has been demonstrated by Aivo et al [18] in MS patients. On top of this, Rollnik et al [28] illuminated that the expression level of TGF-β1 had declined in MS patients' sera compared with the control group and Ishikawa et al [29] confirmed that TGF-β1 was able to improve clinical EAE and inhibit relapse phase in them.…”

“…Vitamin D 3 could both directly and indirectly, upregulate the expression of IL-27 and TGF-β1. All the same, they are not enough and need to clarify more the precise role of vitamin D 3 in regulating them [13,18,19].…”

The Modulatory Effects of Vitamin D on the Expression of IL-12 and TGF-β in the Spinal Cord and Serum of Mice with Experimental Autoimmune Encephalomyelitis

“…In agreement with our findings, mRNA expression of TGF-β and its serum levels were increased after vitamin D supplementation in patients with MS, while EDSS scores decreased (35,36). TGF-β is required for both Th17-and Treg cells differentiation.…”