Glucosylceramide in T cells regulates the pathology of inflammatory bowel disease

Mariko Komuro; Masaki Nagane; Rikito Endo; Takashi Nakamura; Takayoshi Miyamoto; Chiaki Niwa; Tomoki Fukuyama; Hideyoshi Harashima; Naoyuki Aihara; Junichi Kamiie; Rimina Suzuki; Tadashi Yamashita

doi:10.1016/j.bbrc.2022.02.004

Glucosylceramide in T cells regulates the pathology of inflammatory bowel disease

Biochem Biophys Res Commun. 2022 Apr 9:599:24-30. doi: 10.1016/j.bbrc.2022.02.004. Epub 2022 Feb 3.

Affiliations

¹ Laboratory of Biochemistry, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan.
² Laboratory of Biochemistry, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan; Center for Human and Animal Symbiosis Science, Azabu University, Sagamihara, Kanagawa, Japan. Electronic address: nagane@azabu-u.ac.jp.
³ Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.
⁴ Laboratory of Pharmacology, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan.
⁵ Laboratory of Veterinary Pathology, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan.

PMID: 35168060
DOI: 10.1016/j.bbrc.2022.02.004

Abstract

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.

Keywords: Drug delivery system; Glucosylceramide; Lipid nanoparticle; T cell; UDP-Glucose ceramide glucosyltransferase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Colitis / chemically induced
Colitis / drug therapy
Colitis / pathology
Dextran Sulfate / toxicity
Disease Models, Animal
Glucosylceramides / administration & dosage
Glucosylceramides / genetics
Glucosylceramides / metabolism*
Glucosyltransferases / genetics
Glucosyltransferases / metabolism*
Humans
Inflammatory Bowel Diseases / metabolism
Inflammatory Bowel Diseases / pathology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Nanoparticles / administration & dosage
Nanoparticles / chemistry
T-Lymphocytes / metabolism*
T-Lymphocytes / pathology

Substances

Glucosylceramides
Dextran Sulfate
Glucosyltransferases
ceramide glucosyltransferase