Glucosylceramide in T cells regulates the pathology of inflammatory bowel disease.
Animals
Colitis
/ chemically induced
Dextran Sulfate
/ toxicity
Disease Models, Animal
Glucosylceramides
/ administration & dosage
Glucosyltransferases
/ genetics
Humans
Inflammatory Bowel Diseases
/ metabolism
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Nanoparticles
/ administration & dosage
T-Lymphocytes
/ metabolism
Drug delivery system
Glucosylceramide
Lipid nanoparticle
T cell
UDP-Glucose ceramide glucosyltransferase
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
09 04 2022
09 04 2022
Historique:
received:
24
12
2021
accepted:
01
02
2022
pubmed:
16
2
2022
medline:
18
3
2022
entrez:
15
2
2022
Statut:
ppublish
Résumé
Inflammatory bowel disease (IBD) is a chronic inflammatory disease in the colon characterized by excessive activation of T cells. Glycosphingolipids (GSLs) are composed of lipid rafts in cellular membranes, and their content is linked to immune cell function. In the present study, we investigated the involvement of GSLs in IBD. Microarray data showed that in IBD patients, the expression of only UDP-glucose ceramide glucosyltransferase (UGCG) decreased among the GSLs synthases. Ad libitum access to dextran sulfate sodium (DSS) resulted in decreased UGCG and glucosylceramide (GlcCer) content in mesenteric lymph nodes and T cells from the spleen. Furthermore, the knockdown of Ugcg in T cells exacerbated the pathogenesis of colitis, which was accompanied by a decrease in Treg levels. Treatment with GlcCer nanoparticles prevented DSS-induced colitis. These results suggested that GlcCer in T cells is involved in the pathogenesis of IBD. Furthermore, GlcCer nanoparticles are a potential efficacious therapeutic target for IBD patients.
Identifiants
pubmed: 35168060
pii: S0006-291X(22)00180-2
doi: 10.1016/j.bbrc.2022.02.004
pii:
doi:
Substances chimiques
Glucosylceramides
0
Dextran Sulfate
9042-14-2
Glucosyltransferases
EC 2.4.1.-
ceramide glucosyltransferase
EC 2.4.1.80
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
24-30Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest Azabu University and Hokkaido University hold patents on the usage of GlcCer nanoparticles. MK, MN, ER, TN, and TY are the inventors in these patents. Remaining authors do not declare any competing interest.