University of Utah School of Medicine, Department of Pathology, Division of Microbiology and Immunology, Salt Lake City, UT 84112, USA.
University of South Carolina School of Medicine, Department of Pathology, Microbiology and Immunology, Columbia, SC 29209, USA.
Cell Rep. 2021 Nov 2;37(5):109916. doi: 10.1016/j.celrep.2021.109916.
Intestinal epithelial cells (IECs) have long been understood to express high levels of major histocompatibility complex class II (MHC class II) molecules but are not considered canonical antigen-presenting cells, and the impact of IEC-MHC class II signaling on gut homeostasis remains enigmatic. As IECs serve as the primary barrier between underlying host immune cells, we reasoned that IEC-intrinsic antigen presentation may play a role in responses toward the microbiota. Mice with an IEC-intrinsic deletion of MHC class II (IEC) are healthy but have fewer microbial-bound IgA, regulatory T cells (Tregs), and immune repertoire selection. This was associated with increased interindividual microbiota variation and altered proportions of two taxa in the ileum where MHC class II on IECs is highest. Intestinal mononuclear phagocytes (MNPs) have similar MHC class II transcription but less surface MHC class II and are capable of acquiring MHC class II from IECs. Thus, epithelial-myeloid interactions mediate development of adaptive responses to microbial antigens within the gastrointestinal tract.
肠上皮细胞 (IECs) 长期以来被认为表达高水平的主要组织相容性复合体 II 类 (MHC II 类) 分子，但不被认为是经典的抗原提呈细胞，IEC-MHC II 信号对肠道稳态的影响仍然是个谜。由于 IECs 作为潜在宿主免疫细胞之间的主要屏障，我们推测 IEC 内在的抗原提呈可能在针对微生物组的反应中发挥作用。MHC II 类 (IEC) 内在缺失的 IEC 小鼠是健康的，但微生物结合的 IgA、调节性 T 细胞 (Tregs) 和免疫反应选择较少。这与个体间微生物群变异增加以及回肠中 MHC II 类最多的两个分类群的比例改变有关。肠道单核吞噬细胞 (MNPs) 具有相似的 MHC II 类转录，但表面 MHC II 类较少，并且能够从 IEC 获得 MHC II 类。因此，上皮-髓样细胞相互作用介导了胃肠道内对微生物抗原的适应性反应的发展。
