Tongue immune compartment analysis reveals spatial macrophage heterogeneity [bulk RNA-Seq]

The tongue is a unique muscular organ situated in the oral cavity where it is involved in taste sensation, mastication and articulation. As a barrier organ, which is constantly exposed to environmental pathogens,the tongue is expected to host an immune cell network ensuring local immune defense. However, the composition and the transcriptional landscape of the tongue immune system are currently not completely defined. Here we characterized the tissue-resident immune compartment of the murine tongue during development, health and disease, combining single cell RNA-sequencing with in situ immunophenotyping. We identified distinct local immune cell populations and described two specific subsets of tongue-resident macrophages occupying discrete anatomical niches. Cx3cr1+macrophages were located specifically in the highly innervated lamina propria beneath the tongue epidermis and at times in close proximity to fungiform papillae.Folr2+ macrophages were detected in deeper muscular tissue. The two macrophage subsets originate from a common proliferative precursor during early postnatal development and responded differently to systemic LPS in vivo. Our description of the under-investigated tongue immune system sets a starting point to facilitate research on tongue immune-physiology and pathology including cancer and taste disorders. 4 samples舌是位于口腔内的独特肌性器官，参与味觉感知、咀嚼及语音构音。作为持续暴露于环境病原体的屏障器官，舌理应具备维持局部免疫防御的免疫细胞网络。然而，目前学界对舌免疫系统的组成及转录图谱尚未完全阐明。本研究结合单细胞RNA测序（single cell RNA-sequencing）与原位免疫表型分析，对小鼠舌在发育、健康及疾病状态下的组织驻留免疫区室开展了系统表征。研究团队鉴定出多种独特的局部免疫细胞群，并描述了两类占据不同解剖微环境的舌驻留巨噬细胞特异性亚群：CX3CR1+巨噬细胞特异性定位于舌上皮下方的高神经支配固有层，部分紧邻菌状乳头；FOLR2+巨噬细胞则分布于较深层肌肉组织中。这两类巨噬细胞亚群在出生后早期发育阶段均源自共同的增殖前体细胞，并在体内对系统性脂多糖（lipopolysaccharide, LPS）呈现出不同的应答模式。本研究对此前研究不足的舌免疫系统进行的系统性描述，可为舌免疫生理学以及涵盖癌症与味觉障碍在内的舌病理生理学研究提供重要基础。本研究共纳入4个样本。