Loss of the branched-chain amino acid transporter CD98hc alters the development of colonic macrophages in mice
Philipp Wuggenig, Berna Kaya, Hassan Melhem, C. Korcan Ayata, Swiss IBD Cohort Investigators, Karim Abdelrahman, Gentiana Ademi, Patrick Aepli, Claudia Anderegg, Anca-Teodora Antonino, Eva Archanioti, Eviano Arrigoni, Diana Bakker de Jong, Bruno M. Balsiger, Polat Bastürk, Peter Bauerfeind, Andrea Becocci, Dominique C. Belli, José M. Bengoa, Luc Biedermann, Janek Binek, Mirjam Blattmann, Stephan Boehm, Tujana Boldanova, Jan Borovicka, Christian Braegger, Stephan Brand, Lukas Brügger, Simon Brunner, Patrick Bühr, Sabine Burk, Bernard Burnand, Emanuel Burri, Sophie Buyse, Dahlia-Thao Cao, Ove Carstens, Dominique Criblez, Sophie Cunningham, Fabrizia D’Angelo, Philippe de Saussure, Lukas Degen, Joakim Delarive, Christopher Doerig, Barbara Dora, Susan Drerup, Mara Egger, Ali El-Wafa, Matthias Engelmann, Jessica Ezri, Christian Felley, Markus Fliegner, Nicolas Fournier, Montserrat Fraga, Yannick Franc, Remus Frei, Pascal Frei, Michael Fried, Florian Froehlich, Raoul I. Furlano, Luca Garzoni, Martin Geyer, Laurent Girard, Marc Girardin, Delphine Golay, Ignaz Good, Ulrike Graf Bigler, Beat Gysi, Johannes Haarer, Marcel Halama, Janine Haldemann, Pius Heer, Benjamin Heimgartner, Beat Helbling, Peter Hengstler, Denise Herzog, Cyrill Hess, Roxane Hessler, Klaas Heyland, Thomas Hinterleitner, Claudia Hirschi, Petr Hrúz, Pascal Juillerat, Stephan Kayser, Céline Keller, Carolina Khalid-de Bakker, Christina Knellwolf, Christoph Knoblauch, Henrik Köhler, Rebekka Koller, Claudia Krieger, Patrizia Künzler‐Heule, Rachel Kusche, Frank Serge Lehmann, Andrew J. Macpherson, Michel H. Maillard, Michael Manz, Astrid Marot, Rémy Meier, Christa Meyenberger, Pamela A. Meyer
Abstract
Abstract 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.