Glucosylceramide in T cells regulates the pathology of inflammatory bowel disease

• DOI: 10.1016/j.bbrc.2022.02.004
• Publication Date: 2022-02-03T16:17:51Z
• Authors: Mariko Komuro; Masaki Nagane; Rikito Endo; Takashi Nakamura; Takayoshi Miyamoto; Chiaki Niwa; Tomoki Fukuyama; Hideyoshi Harashima; Naoyuki Aihara; Junichi Kamiie; Rimina Suzuki; Tadashi Yamashita
• Keywords: Mice, Knockout; 0301 basic medicine; T-Lymphocytes; Dextran Sulfate; Mice, Transgenic; Colitis; Glucosylceramides; Inflammatory Bowel Diseases; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; 03 medical and health sciences; Glucosyltransferases; Animals; Humans; Nanoparticles

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.