Lipids, Lymphocytes, and Vitamin D
Lipids, Lymphocytes, and Vitamin D
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison
Multiple Sclerosis: Lipids, Lymphocytes, and Vitamin D
https://pubmed.ncbi.nlm.nih.gov/32528735/
Abstract
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. We review the two core MS features, myelin instability, fragmentation, and remyelination failure, and dominance of pathogenic CD4+ Th17 cells over protective CD4+ Treg cells. To better understand myelin pathology, we describe myelin biosynthesis, structure, and function, then highlight stearoyl-CoA desaturase (SCD) in nervonic acid biosynthesis and nervonic acid's contribution to myelin stability. Noting that vitamin D deficiency decreases SCD in the periphery, we propose it also decreases SCD in oligodendrocytes, disrupting the nervonic acid supply and causing myelin instability and fragmentation. To better understand the distorted Th17/Treg cell balance, we summarize Th17 cell contributions to MS pathogenesis, then highlight how 1,25-dihydroxyvitamin D3 signaling from microglia to CD4+ T cells restores Treg cell dominance. This signaling rapidly increases flux through the methionine cycle, removing homocysteine, replenishing S-adenosyl-methionine, and improving epigenetic marking. Noting that DNA hypomethylation and inappropriate DRB1*1501 expression were observed in MS patient CD4+ T cells, we propose that vitamin D deficiency thwarts epigenetic downregulation of DRB1*1501 and Th17 cell signature genes, and upregulation of Treg cell signature genes, causing dysregulation within the CD4+ T cell compartment. We explain how obesity reduces vitamin D status, and how estrogen and vitamin D collaborate to promote Treg cell dominance in females. Finally, we discuss the implications of this new knowledge concerning myelin and the Th17/Treg cell balance, and advocate for efforts to address the global epidemics of obesity and vitamin D deficiency in the expectation of reducing the impact of MS.
-
- Similar Topics
- Replies
- Views
- Last post
-
- 0 Replies
- 184 Views
-
Last post by frodo
Tue Jul 21, 2020 1:18 am
-
-
MS linked to lipids dysregulation
by frodo » Mon Dec 02, 2019 11:26 am » in MS Etiology and Pathogenesis - 1 Replies
- 642 Views
-
Last post by Anonymoose
Wed Dec 04, 2019 6:10 am
-
-
-
lipids differentiate PPMS and SPMS
by frodo » Fri Oct 02, 2020 4:47 am » in MS Etiology and Pathogenesis - 0 Replies
- 267 Views
-
Last post by frodo
Fri Oct 02, 2020 4:47 am
-
-
-
Twins comparison suggest lipids metabolism implications
by frodo » Thu Nov 12, 2020 4:04 am » in MS Etiology and Pathogenesis - 0 Replies
- 239 Views
-
Last post by frodo
Thu Nov 12, 2020 4:04 am
-
-
- 2 Replies
- 569 Views
-
Last post by jimmylegs
Mon Nov 16, 2020 4:27 am
-
- 1 Replies
- 6673 Views
-
Last post by Zyklon
Tue Aug 13, 2019 8:56 am
-
-
Vitamin D3's anti-inflammatory effect via IL-27 & TGF-B1
by NHE » Thu Jan 14, 2021 2:09 am » in Natural Approach - 0 Replies
- 246 Views
-
Last post by NHE
Thu Jan 14, 2021 2:09 am
-
-
-
The Effect of Vitamin B12 and Folic Acid
by Petr75 » Tue Mar 12, 2019 11:35 am » in General Discussion - 0 Replies
- 863 Views
-
Last post by Petr75
Tue Mar 12, 2019 11:35 am
-
-
-
High dose vitamin D exacerbates CNS autoimmunity
by Petr75 » Sat Sep 21, 2019 11:15 am » in Coimbra High-Dose Vitamin D Protocol - 3 Replies
- 1622 Views
-
Last post by clarentine
Sat Oct 05, 2019 10:11 am
-