Co-Stimulation-Impaired Bone Marrow-Derived Dendritic Cells Prevent Dextran Sodium Sulfate-Induced Colitis in Mice

Frontiers in Immunology
Carl EngmanNick Giannoukakis

Abstract

Dendritic cells (DC) are important in the onset and severity of inflammatory bowel disease (IBD). Tolerogenic DC induce T-cells to become therapeutic Foxp3+ regulatory T-cells (Tregs). We therefore asked if experimental IBD could be prevented by administration of bone marrow-derived DC generated under conventional GM-CSF/IL-4 conditions but in the presence of a mixture of antisense DNA oligonucleotides targeting the primary transcripts of CD40, CD80, and CD86. These cell products (which we call AS-ODN BM-DC) have demonstrated tolerogenic activity in preventing type 1 diabetes and preserving beta cell mass in new-onset type 1 diabetes in the NOD mouse strain, in earlier studies. In addition to measuring efficacy in prevention of experimental IBD, we also sought to identify possible mechanism(s) of action. Weight, behavior, stool frequency, and character were observed daily for 7-10 days in experimental colitis in mice exposed to dextran sodium sulfate (DSS) following injection of the AS-ODN BM-DC. After euthanasia, the colons were processed for histology while spleen and mesenteric lymph nodes (MLNs) were made into single cells to measure Foxp3+ Treg as well as IL-10+ regulatory B-cell (Breg) population frequency by flow cytomet...Continue Reading

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Citations

Aug 25, 2019·Journal of the American Society of Nephrology : JASN·Dragana OdobasicStephen R Holdsworth
Aug 12, 2020·Life Sciences·Fei HanXiaolan Zhang
Aug 8, 2021·International Journal of Molecular Sciences·Shaghayegh Baradaran GhavamiMohammad Reza Zali
Aug 17, 2021·Frontiers in Immunology·Dragana Odobasic, Stephen R Holdsworth

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Methods Mentioned

BETA
antisense oligonucleotides
antisense oligonucleotide
flow cytometry
FACS
ELISA
transgenic
biopsies

Clinical Trials Mentioned

NCT02622763

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