Loss of the branched-chain amino acid transporter CD98hc alters the development of colonic macrophages in mice
| Autor: | Wuggenig, Philipp, Kaya, Berna, Melhem, Hassan, Ayata, C Korcan, Swiss IBD Cohort Investigators, Hruz, Petr, Sayan, A Emre, Tsumura, Hideki, Ito, Morihiro, Roux, Julien, Niess, Jan Hendrik, Marot, Astrid |
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| Přispěvatelé: | UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Adolescent Fusion Regulatory Protein 1 Heavy Chain Colon CX3C Chemokine Receptor 1 Apoptosis Article Inflammatory bowel disease Young Adult Crohn Disease Animals Humans RNA-Seq Intestinal Mucosa Aged Aged 80 and over Mice Knockout Macrophages Dextran Sulfate Middle Aged Colitis Mice Inbred C57BL Disease Models Animal Phenotype Gene Expression Regulation Mucosal immunology Colitis Ulcerative Female Single-Cell Analysis Apoptosis Regulatory Proteins Amino Acids Branched-Chain |
| Zdroj: | Communications biology, Vol. 3, no. 1, p. 130 (2020) Communications Biology |
| Popis: | Comprehensive development is critical for gut macrophages being essential for the intestinal immune system. However, the underlying mechanisms of macrophage development in the colon remain elusive. To investigate the function of branched-chain amino acids in the development of gut macrophages, an inducible knock-out mouse model for the branched-chain amino acid transporter CD98hc in CX3CR1+ macrophages was generated. The relatively selective deletion of CD98hc in macrophage populations leads to attenuated severity of chemically-induced colitis that we assessed by clinical, endoscopic, and histological scoring. Single-cell RNA sequencing of colonic lamina propria macrophages revealed that conditional deletion of CD98hc alters the “monocyte waterfall”-development to MHC II+ macrophages. The change in the macrophage development after deletion of CD98hc is associated with increased apoptotic gene expression. Our results show that CD98hc deletion changes the development of colonic macrophages. CD98hc in macrophages attenuates the severity of colitis. This change in the macrophage development is associated with increased expression of apoptotic genes, suggesting that CD98hc maintains the gut homeostasis by ensuring the development of gut macrophages. |
| Databáze: | OpenAIRE |
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