Polar functional group-containing glycolipid CD1d ligands modulate cytokine-biasing responses and prevent experimental colitis

Shinsuke Inuki, Natsumi Hirata, Emi Kashiwabara, Junichiro Kishi, Toshihiko Aiba, Toshiaki Teratani, Wataru Nakamura, Yoshimi Kojima, Toru Maruyama, Takanori Kanai, Yukari Fujimoto

研究成果: Article査読

9 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号15766
ジャーナルScientific reports
10
1
DOI
出版ステータスPublished - 2020 12月 1

ASJC Scopus subject areas

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