Loss of the branched-chain amino acid transporter CD98hc alters the development of colonic macrophages in mice

Publikation

Loss of the branched-chain amino acid transporter CD98hc alters the development of colonic macrophages in mice

Wissenschaftlicher Artikel/Review - 18.03.2020

Wuggenig Philipp, Roux Julien, Ito Morihiro, Tsumura Hideki, Sayan A Emre, Hruz Petr, Swiss IBD Cohort Investigators, Ayata C Korcan, Melhem Hassan, Kaya Berna, Niess Jan Hendrik

PubMed

32188932

DOI

10.1038/s42003-020-0842-3

Zitation

Wuggenig P, Roux J, Ito M, Tsumura H, Sayan A, Hruz P, Swiss IBD Cohort Investigators, Ayata C, Melhem H, Kaya B, Niess J. Loss of the branched-chain amino acid transporter CD98hc alters the development of colonic macrophages in mice. Commun Biol 2020; 3:130.

Art

Wissenschaftlicher Artikel/Review (Englisch)

Zeitschrift

Commun Biol 2020; 3

Veröffentlichungsdatum

18.03.2020

eISSN (Online)

2399-3642

Seiten

130

Kurzbeschreibung/Zielsetzung

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.