20-Hydroxyvitamin D3, a Secosteroid Produced in Humans, Is Anti-Inflammatory and Inhibits Murine Autoimmune Arthritis

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Jul 19

PMID 34276665

Citations 15

Authors

Arnold E Postlethwaite

Robert C Tuckey

Tae-Kang Kim

Wei Li

Syamal K Bhattacharya

Linda K Myers

David D Brand

Andrzej T Slominski

Affiliations

Soon will be listed here.

Abstract

The ability to use large doses of vitamin D3 (D3) to chronically treat autoimmune diseases such as rheumatoid arthritis (RA) is prohibitive due to its calcemic effect which can damage vital organs. Cytochrome P450scc (CYP11A1) is able to convert D3 into the noncalcemic analog 20-hydroxyvitamin D3 [20(OH)D3]. We demonstrate that 20(OH)D3 markedly suppresses clinical signs of arthritis and joint damage in a mouse model of RA. Furthermore, treatment with 20(OH)D3 reduces lymphocyte subsets such as CD4 T cells and CD19 B cells leading to a significant reduction in inflammatory cytokines. The ratio of T reg cells (CD4+CD25+Foxp3+ T cells) to CD3+CD4+ T cells is increased while there is a decrease in critical complement-fixing anti-CII antibodies. Since pro-inflammatory cytokines and antibodies against type II collagen ordinarily lead to destruction of cartilage and bone, their decline explains why arthritis is attenuated by 20(OH) D3. These results provide a basis for further consideration of 20(OH)D3 as a potential treatment for RA and other autoimmune disorders.

Citing Articles

Biological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin.

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Novel Vitamin D3 Hydroxymetabolites Require Involvement of the Vitamin D Receptor or Retinoic Acid-Related Orphan Receptors for Their Antifibrogenic Activities in Human Fibroblasts.

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Tumors produce glucocorticoids by metabolite recycling, not synthesis, and activate Tregs to promote growth.

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A Systematic Review Assessing the Impact of Vitamin D Levels on Adult Patients with Lymphoid Malignancies.

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