Vitamin A Promotes the Fusion of Autophagolysosomes and Prevents Excessive Inflammasome Activation in Dextran Sulfate Sodium-Induced Colitis

• Published in: International journal of molecular sciences Vol. 24; no. 10; p. 8684
• Main Authors: Hiraga, Hiroto, Chinda, Daisuke, Maeda, Takato, Murai, Yasuhisa, Ogasawara, Kohei, Muramoto, Ryutaro, Ota, Shinji, Hasui, Keisuke, Sakuraba, Hirotake, Ishiguro, Yoh, Yoshida, Shukuko, Asano, Krisana, Nakane, Akio, Fukuda, Shinsaku
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12-05-2023; MDPI
• Subjects: Acids; Animal models; Animals; Autophagy; B cells; Colitis; Colitis - metabolism; Cristae; Cytokines; Dextran; Dextran sulfate; Dextran Sulfate - toxicity; Dextrans; Diet therapy; Disease Models, Animal; Electron microscopy; Homeostasis; Immunodeficiency; Inflammasomes; Inflammasomes - metabolism; Inflammatory bowel disease; Inflammatory diseases; Innate immunity; Lamina propria; Lymphocytes B; Lysosomes; Lysosomes - metabolism; Macrophages; Mice; Mice, Inbred C57BL; Mitochondria; Mutation; Phagosomes; Prevention; Proteins; Pyroptosis; Retinene; Retinoic acid; Scientific equipment and supplies industry; Sodium; Sulfates; Tumor necrosis factor-TNF; Vitamin A; Vitamin A - pharmacology; Vitamin deficiency; United States; Japan; pyroptosis; retinoic acid; autophagy; vitamin A; inflammatory bowel disease
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24108684

Vitamin A ensures intestinal homeostasis, impacting acquired immunity and epithelial barrier function; however, its role in innate immunity is mostly unknown. Here, we studied the impact of vitamin A in different dextran sulfate sodium (DSS)-induced colitis animal models. Interestingly, more severe DSS-induced colitis was observed in vitamin A-deficient (VAD) mice than in vitamin A-sufficient (VAS) mice; the same was observed in VAD severe combined immunodeficient mice lacking T/B cells. Remarkably, IL-1β production, LC3B-II expression, and inflammasome activity in the lamina propria were significantly elevated in VAD mice. Electron microscopy revealed numerous swollen mitochondria with severely disrupted cristae. In vitro, non-canonical inflammasome signaling-induced pyroptosis, LC3B-II and p62 expression, and mitochondrial superoxide levels were increased in murine macrophages (RAW 264.7) pretreated with retinoic acid receptor antagonist (Ro41-5253). These findings suggest that vitamin A plays a crucial role in the efficient fusion of autophagosomes with lysosomes in colitis.