Polar functional group-containing glycolipid CD1d ligands modulate cytokine-biasing responses and prevent experimental colitis
| Autor: | Yoshimi Kojima, Toru Maruyama, Yukari Fujimoto, Shinsuke Inuki, Emi Kashiwabara, Toshiaki Teratani, Wataru Nakamura, Takanori Kanai, Junichiro Kishi, Toshihiko Aiba, Natsumi Hirata |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Carbohydrates lcsh:Medicine Galactosylceramides Drug development chemical and pharmacologic phenomena Ligands Article Mice Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine Glycolipid In vivo MHC class I medicine Animals Structure–activity relationship lcsh:Science Multidisciplinary biology Chemistry lcsh:R T-cell receptor Water Natural killer T cell carbohydrates (lipids) Disease Models Animal 030104 developmental biology Cytokine Solubility Biochemistry Drug Design 030220 oncology & carcinogenesis CD1D biology.protein Cytokines Colitis Ulcerative lcsh:Q lipids (amino acids peptides and proteins) Antigens CD1d Glycolipids |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-72280-4 |
| Popis: | The MHC class I-like molecule CD1d is a nonpolymorphic antigen-presenting glycoprotein, and its ligands include glycolipids, such as α-GalCer. The complexes between CD1d and ligands activate natural killer T cells by T cell receptor recognition, leading to the secretion of various cytokines (IFN-γ, IL-4, IL-17A, etc.). Herein, we report structure–activity relationship studies of α-GalCer derivatives containing various functional groups in their lipid acyl chains. Several derivatives have been identified as potent CD1d ligands displaying higher cytokine induction levels and/or unique cytokine polarization. The studies also indicated that flexibility of the lipid moiety can affect the binding affinity, the total cytokine production level and/or cytokine biasing. Based on our immunological evaluation and investigation of physicochemical properties, we chose bisamide- and Bz amide-containing derivatives 2 and 3, and evaluated their in vivo efficacy in a DSS-induced model of ulcerative colitis. The derivative 3 that exhibits Th2- and Th17-biasing responses, demonstrated significant protective effects against intestinal inflammation in the DSS-induced model, after a single intraperitoneal injection. |
| Databáze: | OpenAIRE |
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