Table 2.
Preclinical studies with vitamin D supplementation
| Reference | Experimental model | Mechanism of VitD action |
|---|---|---|
| Lemire and Archer, 1991; Cantorna et al., 1996 | SJL/J and B10.PL mice | VitD prevented the induction and blocked the progression of relapsing EAE. |
| Cantorna et al., 1998 | B10.PL mice | Increased the levels of IL-4 and TGF-β1 transcripts in LN and CNS. |
| Mattner et al., 2000 | Biozzi AB/H mice | Reduced T cell proliferation and lower IFN-γ levels in popliteal LN. |
| Reduced the inflammatory infiltrates, demyelinated areas and axonal loss in brains and spinal cords. | ||
| Nashold et al., 2000 | B10.PL mice | Decreased macrophage accumulation in the CNS. |
| Meehan and DeLuca, 2002 | VDR null and B10.PL mice | VDR was necessary for preventing the onset of EAE development. |
| Muthian et al., 2006 | C57BL/6 and SJL/J mice | Inhibited JAK-STAT pathway in IL-12/IFN-γ axis leading to differentiation of neural antigen-specific Th1 cells. |
| Spach et al., 2006 | C57BL/6 and SJL/J mice with a disrupted IL-10 or IL-10R gene | Protective mechanism required a functional IL-10-IL-10R pathway. |
| Chang et al., 2010 | BALB/c, C57BL/6 mice, Rag2−/− DO11.10, MOG-TCR (2D2), IL-10−/− and STAT1−/− transgenic mice | Down-regulated CCR6 expression, inhibited the differentiation and migration of Th17 cells to the CNS. Reduced the total infiltration of CD4+ T cells in the CNS. |
| Sloka et al., 2011 | C57BL/6 and STAT6−/− mice | Increased the levels of GATA-3 and STAT6. |
| Grishkan et al., 2013 | C57BL/6, CD45.1+, B6(Cg)-Tyrc-2J/J and 2D2 mice | Impaired Th cell migration into the CNS and reduced the expression of the chemokine receptor CXCR3 on Th cells. |
| Li et al., 2013 | C57BL/6 mice | Reduced the inflammatory cell infiltration, inflammatory cytokine (TNF-a, INF-γ and IL-17) and TLR8 expression in the CNS. |
| Nashold et al., 2013 | B10.PL mice | Increased Helios+FoxP3+ T cells in the CNS. |
| Mohammadi-Kordkhayli et al., 2015 | C57BL/6 mice | Down-modulated the expression of IL-27 and IL-33 in the CNS. |
| Sloka et al., 2015 | C57BL/6 mice | Reduced the axonal and neuronal loss. |
| Waddell et al., 2015 | Jα18−/−, CD1d−/−, IL-4−/− and WT C57BL/6 mice | Protection from EAE mediated by VitD was partially regulated by NKT cells. |
| Zhen et al., 2015 | C57BL/6 mice | Impaired autophagic activity and neuroapoptosis, characterized by elevated expression of Beclin1, increased Bcl-2/Bax ratio, and decreased LC3-II accumulation. |
| Shirazi et al., 2017 | C57BL/6 mice | Increased the numbers of neural stem cells, oligodendrocyte precursor cells, and oligodendrocytes in disease lesions in the CNS. |
| Ahangar-Parvin et al., 2018 | C57BL/6 mice | Down-modulated IL-12 and TGF-β expression in the CNS and serum. |
| Hoepner et al., 2019 | C57BL/6 and BALB/c WT mice and danimals with altered GR signaling | Increased glucocorticoid efficacy via inhibition of mTORC1. |
| Jafarzadeh et al., 2019 | C57BL/6 mice | Down-regulated the expression of some Th17 cell-related cytokines, key inflammatory chemokines, and chemokine receptors in the CNS (IL-17, IL-23 P19, IL-23 P40, CCL20, CCL22 and CCR4). |
| de Oliveira et al., 2020 | C57BL/6 mice | Prevented neuroinflammation and reduced blood-brain barrier disruption and local macrophage/microglia activation. |
| Reduced the oxidative stress and expression of NLRP3, caspase-1, IL-1β, CX3CR1, CCL17, RORc and Tbx21 in the CNS. | ||
| Gomez-Pinedo et al., 2020 | Wistar rats | Increased remyelination by promoting oligodendrocyte lineage differentiation. |
| Spanier et al., 2020 | C57BL/6 and B6. Lyz2-Cre+Cyp27b1f/f mice | Increased CTLA-4 expression by spinal cord-infiltrating CD4+ T and Treg cells. |
| Mimura et al., 2021 | C57BL/6 mice | Reduced the expression of inflammatory parameters, and demyelination at the CNS |
| Down-regulated the proinflammatory cytokines production by lymph node-derived cells and IL-17 by gut explants and reduced intestinal inflammation. |
CCL: Chemokine ligand; CCR: chemokine receptor; CD: cluster of differentiation; CNS: central nervous system; CTLA: cytotoxic T-lymphocyte associated protein; EAE: experimental autoimmune encephalomyelitis; FoxP3: forkhead box P3; GR: glucocorticoid receptor; IFN: interferon; IL: interleukin; JAK: Janus kinase; LC3: microtubule-associated protein light chain 3; LN: lymph node; MOG: myelin oligodendrocyte glycoprotein; mTOR: mammalian target of rapamycin; NKT: natural Killer T cell; NLRP: nucleotide-biding oligomerization domain, leucine rich repeat and pyrin domain containing; STAT: signal transducer and activator of transcription; TGF: transforming growth factor; Th: T helper cell; TLR: toll-like receptor; TNF: tumor necrosis factor; Treg: regulatory T cell; VDR: vitamin D receptor; VitD: vitamin D; WT: wild-type.