Glucosylceramide in T cells regulates the pathology of inflammatory bowel disease

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

doi:10.1016/j.bbrc.2022.02.004

Cited by 8 publications

(11 citation statements)

References 34 publications

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“…In IBD patients and in a DSS induced colitis mouse model UGCG activity was decreased, and knockdown of UGCG resulted in Treg decrease and CD4 effector cell increase ( Table1 ). In line with this, intravenouse application of nanoparticles loaded with glucosylceramide (GluCer) into DSS treated mice improved colitis symptomes in these mice and enhaced Treg cells in spleen and colon ( Komuro et al, 2022 ). These data indicate that Treg development and function depends on different sphingolipids that impact activation and differentiation of Tregs at various cell stages.…”

Section: The Impact Of Sphingolipids On T Cells and Their Role In Res...mentioning

confidence: 74%

“…A particular sphingolipid composition of the membrane seems to be required for the different subsets of T cells and the formation of variable immunological synapses. For this reason sphingolipids influence diverse chronic inflammatory diseases that are driven by Th1 or Th2 cell response, and an imbalance between Th17 and Tregs such as in rheumatoid arthritis ( Tsukuda et al, 2012 ) or IBD patients ( Komuro et al, 2022 ) and are important for the resolution of inflammation. So, in future studies enzymes of the sphingolipid pathway as well as sphingolipids themselves should be considered as new possible targets to boost resolving processes and to dampen pro-inflammatory mechanisms.…”

Section: Discussionmentioning

confidence: 99%

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How sphingolipids affect T cells in the resolution of inflammation

2022

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The concept of proper resolution of inflammation rather than counteracting it, gained a lot of attention in the past few years. Re-assembly of tissue and cell homeostasis as well as establishment of adaptive immunity after inflammatory processes are the key events of resolution. Neutrophiles and macrophages are well described as promotors of resolution, but the role of T cells is poorly reviewed. It is also broadly known that sphingolipids and their imbalance influence membrane fluidity and cell signalling pathways resulting in inflammation associated diseases like inflammatory bowel disease (IBD), atherosclerosis or diabetes. In this review we highlight the role of sphingolipids in T cells in the context of resolution of inflammation to create an insight into new possible therapeutical approaches.

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Section: The Impact Of Sphingolipids On T Cells and Their Role In Res...mentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

How sphingolipids affect T cells in the resolution of inflammation

2022

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“…To induce colitis, mice were administered 2% (w/v) dextran sulfate sodium (DSS, Cat No. 199‐08361, Wako Pure Chemical Industries, Osaka, Japan) in sterile drinking water, which was provided ad libitum as described previously 16 . The DSS group was fed a normal diet.…”

Section: Methodsmentioning

confidence: 99%

“…Spleens were collected from mice, mechanically disrupted, and isolated splenocytes were stained as described previously. 16 The antibodies used for flow cytometry are listed in Table 2. For Treg(s) staining, the Treg Detection Kit (catalog no.…”

Section: Flow Cytometrymentioning

confidence: 99%

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The novel sustained 3‐hydroxybutyrate donor poly‐D ‐3‐hydroxybutyric acid prevents inflammatory bowel disease through upregulation of regulatory T‐cells

et al. 2022

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Inflammatory bowel disease (IBD) is a chronic persistent intestinal disorder, with ulcerative colitis and Crohn's disease being the most common. However, the physio-pathological development of IBD is still unknown. Therefore, research on the etiology and treatment of IBD has been conducted using a variety of approaches. Short-chain fatty acids such as 3-hydroxybutyrate (3-HB) are known to have various physiological activities. In particular, the production of 3-HB by the intestinal microflora is associated with the suppression of various inflammatory diseases. In this study, we investigated whether poly-D-3-hydroxybutyric acid (PHB), a polyester of 3-HB, is degraded by intestinal microbiota and works as a slow-release agent of 3-HB. Further, we examined whether PHB suppresses the pathogenesis of IBD models. As long as a PHB diet increased 3-HB concentrations in the feces and blood, PHB suppressed weight loss and histological inflammation in a dextran sulfate sodium-induced IBD model. Furthermore, PHB increased the accumulation of regulatory T cells in the rectum without affecting T cells in the spleen. These results indicate that PHB has potential applications in treating diseases related to the intestinal microbiota as a sustained 3-HB donor. We show for the first time that biodegradable polyester exhibits intestinal bacteria-mediated bioactivity toward IBD. The use of bioplastics, which are essential materials for How to cite this article: Suzuki R, Mishima M, Nagane M, et al. The novel sustained 3-hydroxybutyrate donor poly-D-3-hydroxybutyric acid prevents inflammatory bowel disease through upregulation of regulatory T-cells.

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