Endogenous antisense RNA curbs CD39 expression in Crohn’s disease
Abstract
CD39 is an ectonucleotidase that initiates conversion of extracellular nucleotides into immunosuppressive adenosine. CD39 is expressed by regulatory T (Treg)-cells, where it mediates immunosuppression, and by a subset of T-helper (Th) 17-cells, where it limits pathogenicity. CD39 is regulated via single-nucleotide-polymorphisms and upon activation of aryl-hydrocarbon-receptor and oxygen-mediated pathways. Here we report a mechanism of CD39 regulation that relies on the presence of an endogenous antisense RNA, transcribed from the 3′-end of the human CD39/ENTPD1 gene. CD39-specific antisense is increased in Treg and Th17-cells of Crohn’s disease patients over controls. It largely localizes in the cell nucleus and regulates CD39 by interacting with nucleolin and heterogeneous-nuclear-ribonucleoprotein-A1. Antisense silencing results in CD39 upregulation in vitro and amelioration of disease activity in a trinitro-benzene-sulfonic-acid model of colitis in humanized NOD/scid/gamma mice. Inhibition/blockade of antisense might represent a therapeutic strategy to restore CD39 along with immunohomeostasis in Crohn’s disease.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 18, 2020
- Source ID
- 10.1038/s41467-020-19692-y
Entities
People
- Adam S. Cheifetz
- Alan C. Moss
- Anyan Xie
- Barbora Gromova
- Efi Kokkotou
- Eva Csizmadia
- Haohai Zhang
- Luiza Abrahão Frank
- Maria Serena Longhi
- Marta Vuerich
- Rasika P. Harshe
- Rene’ J. Robles
- Samiran Mukherjee
- Satya K. Kota
- Simon C. Robson
Organizations
- American Association for the Study of Liver Diseases
- National Institutes of Health
- United States Department of Defense
- United States Department of Health and Human Services