Loss of the branched-chain amino acid transporter CD98hc alters the development of colonic macrophages in mice
Authors: Wuggenig Philipp , Kaya Berna , Melhem Hassan , Ayata C. Korcan ,   Swiss IBD Cohort Investigators, Abdelrahman Karim , Ademi Gentiana , Aepli Patrick , Anderegg Claudia , Antonino Anca-Teodora , Archanioti Eva , Arrigoni Eviano , de Jong Diana Bakker , Balsiger Bruno , Bastürk Polat , Bauerfeind Peter , Becocci Andrea , Belli Dominique , Bengoa José M. , Biedermann Luc , Binek Janek , Blattmann Mirjam , Boehm Stephan , Boldanova Tujana , Borovicka Jan , Braegger Christian P. , Brand Stephan , Brügger Lukas , Brunner Simon , Bühr Patrick , Burk Sabine , Burnand Bernard , Burri Emanuel , Buyse Sophie , Cao Dahlia-Thao , Carstens Ove , Criblez Dominique H. , Cunningham Sophie , D’Angelo Fabrizia , de Saussure Philippe , Degen Lukas , Delarive Joakim , Doerig Christopher , Dora Barbara , Drerup Susan , Egger Mara , El-Wafa Ali , Engelmann Matthias , Ezri Jessica , Felley Christian , Fliegner Markus , Fournier Nicolas , Fraga Montserrat , Franc Yannick , Frei Remus , Frei Pascal , Fried Michael , Froehlich Florian , Furlano Raoul Ivano , Garzoni Luca , Geyer Martin , Girard Laurent , Girardin Marc , Golay Delphine , Good Ignaz , Bigler Ulrike Graf , Gysi Beat , Haarer Johannes , Halama Marcel , Haldemann Janine , Heer Pius , Heimgartner Benjamin , Helbling Beat , Hengstler Peter , Herzog Denise , Hess Cyrill , Hessler Roxane , Heyland Klaas , Hinterleitner Thomas , Hirschi Claudia , Hruz Petr , Juillerat Pascal , Kayser Stephan , Keller Céline , Khalid-de Bakker Carolina , Knellwolf Christina , Knoblauch Christoph , Köhler Henrik , Koller Rebekka , Krieger Claudia , Künzler Patrizia , Kusche Rachel , Lehmann Frank Serge , Macpherson Andrew J. , Maillard Michel H. , Manz Michael , Marot Astrid , Meier Rémy , Meyenberger Christa , Meyer Pamela , Michetti Pierre , Misselwitz Benjamin , Mosler Patrick , Mottet Christian , Müller Christoph , Müllhaupt Beat , Musso Leilla , Neagu Michaela , Nichita Cristina , Niess Jan H. , Nydegger Andreas , Obialo Nicole , Ollo Diana , Oropesa Cassandra , Peter Ulrich , Peternac Daniel , Petit Laetitia Marie , Pittet Valérie , Pohl Daniel , Porzner Marc , Preissler Claudia , Raschle Nadia , Rentsch Ronald , Restellini Sophie , Restellini Alexandre , Richterich Jean-Pierre , Ris Frederic , Risti Branislav , Ritz Marc Alain , Rogler Gerhard , Röhrich Nina , Rossel Jean-Benoît , Rueger Vanessa , Rusticeanu Monica , Sagmeister Markus , Saner Gaby , Sauter Bernhard , Sawatzki Mikael , Scharl Michael , Schelling Martin , Schibli Susanne , Schlauri Hugo , Schluckebier Dominique , Schmid Sybille , Schmid Daniela , Schnegg Jean-François , Schoepfer Alain , Seematter Vivianne , Seibold Frank , Seirafi Mariam , Semadeni Gian-Marco , Senning Arne , Sokollik Christiane , Sommer Joachim , Spalinger Johannes , Spangenberger Holger , Stadler Philippe , Staub Peter , Staudenmann Dominic , Stenz Volker , Steuerwald Michael , Straumann Alex , Strebel Bruno , Stulz Andreas , Sulz Michael , Tatu Aurora , Tempia-Caliera Michela , Thomas Amman , Thorens Joël , Truninger Kaspar , Tutuian Radu , Urfer Patrick , Vavricka Stephan , Viani Francesco , Vögtlin Jürg , Von Känel Roland , Vouillamoz Dominique , Vulliamy Rachel , Wiesel Paul , Wiest Reiner , Wöhrle Stefanie , Wylie Tina , Zamora Samuel , Zander Silvan , Zeitz Jonas , Zimmermann Dorothee , Hruz Petr , Sayan A. Emre , Tsumura Hideki , Ito Morihiro , Roux Julien , Niess Jan Hendrik 
Published: March 2020

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.