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.

肠道巨噬细胞的全面发育对于肠道免疫系统至关重要。然而，结肠巨噬细胞发育的潜在机制仍然难以捉摸。为了研究支链氨基酸在肠道巨噬细胞发育中的作用，我们建立了 CX3CR1 ⁺巨噬细胞中支链氨基酸转运蛋白 CD98hc 的诱导型敲除小鼠模型。巨噬细胞群中 CD98hc 的相对选择性缺失导致我们通过临床、内窥镜和组织学评分评估的化学诱导结肠炎的严重程度减弱。结肠固有层巨噬细胞的单细胞 RNA 测序显示 CD98hc 的条件性缺失改变了“单核细胞瀑布”-发展为 MHC II ⁺巨噬细胞。CD98hc 缺失后巨噬细胞发育的变化与凋亡基因表达增加有关。我们的结果表明 CD98hc 缺失改变了结肠巨噬细胞的发育。