Mucosal vitamin D signaling in inflammatory bowel disease

Mucosal vitamin D signaling in inflammatory bowel disease:

Publication date: Available online 15 September 2020
Source: Autoimmunity Reviews
Author(s): Lauge Kellermann, Kim Bak Jensen, Fredrik Bergenheim, John Gubatan, Naomi D. Chou, Alan Moss, Ole Haagen Nielsen


Author links open overlay panelLaugeKellermannaKim BakJensenbcFredrikBergenheimaJohnGubatandNaomi D.ChoueAlanMossfOle HaagenNielsena
a
Department of Gastroenterology, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark
b
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, DK-2200 Copenhagen N, Denmark
c
Novo Nordisk Foundation Center for Stem Cell Biology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen N, Denmark
d
Division of Gastroenterology and Hepatology, Dept. of Medicine, Stanford University School of Medicine, Redwood City, CA, USA
e
Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, MA, USA
f
Boston Medical Center & Boston University, Boston, MA, USA
Received 6 May 2020, Accepted 14 May 2020, Available online 15 September 2020.

https://doi.org/10.1016/j.autrev.2020.102672Get rights and content
Highlights
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Low levels of serum vitamin D are associated with adverse clinical outcomes in IBD.

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Vitamin D signaling modulates the intestinal microbiome and immune functions.

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Intestinal barrier integrity is maintained by vitamin D.

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Vitamin D signaling alters the expression of known IBD risk genes.


Abstract
Epidemiological studies have identified vitamin D (25(OH)D) deficiency to be highly prevalent among patients with inflammatory bowel disease (IBD), and low serum levels correlate with a higher disease activity and a more complicated disease course. The link to IBD pathogenesis has been subject of investigations, primarily due to the distinct immunological functions of vitamin D signaling, including anti-inflammatory and anti-fibrotic actions. Vitamin D is a pleiotropic hormone that executes its actions on cells through the vitamin D receptor (VDR). A leaky gut, i.e. an insufficient intestinal epithelial barrier, is thought to be central for the pathogenesis of IBD, and emerging data support the concept that vitamin D/VDR signaling in intestinal epithelial cells (IECs) has an important role in controlling barrier integrity. Here we review the latest evidence on how vitamin D promotes the interplay between IECs, the gut microbiome, and immune cells and thereby regulate the intestinal immune response. On the cellular level, vitamin D signaling regulates tight junctional complexes, apoptosis, and autophagy, leading to increased epithelial barrier integrity, and promotes expression of antimicrobial peptides as part of its immunomodulating functions. Further, intestinal VDR expression is inversely correlated with the severity of inflammation in patients with IBD, which might compromise the positive effects of vitamin D signaling in patients with flaring disease. Efforts to reveal the role of vitamin D in the pathophysiology of IBD will pave the road for the invention of more rational treatment strategies of this debilitating disease in the future.

Keywords
Cell signalingIntestinal barrierInflammatory bowel diseaseVitamin DVitamin D receptor
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