Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Stanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, NY, 10021, USA.
Columbia Center for Translational Immunology, Department of Surgery and Department of Microbiology and Immunology, Columbia University Medical Center, NY, New York, 10032, USA.
Immunity. 2019 Feb 19;50(2):505-519.e4. doi: 10.1016/j.immuni.2019.01.012. Epub 2019 Feb 12.
Innate lymphoid cells (ILC) play critical roles in regulating immunity, inflammation, and tissue homeostasis in mice. However, limited access to non-diseased human tissues has hindered efforts to profile anatomically-distinct ILCs in humans. Through flow cytometric and transcriptional analyses of lymphoid, mucosal, and metabolic tissues from previously healthy human organ donors, here we have provided a map of human ILC heterogeneity across multiple anatomical sites. In contrast to mice, human ILCs are less strictly compartmentalized and tissue localization selectively impacts ILC distribution in a subset-dependent manner. Tissue-specific distinctions are particularly apparent for ILC1 populations, whose distribution was markedly altered in obesity or aging. Furthermore, the degree of ILC1 population heterogeneity differed substantially in lymphoid versus mucosal sites. Together, these analyses comprise a comprehensive characterization of the spatial and temporal dynamics regulating the anatomical distribution, subset heterogeneity, and functional potential of ILCs in non-diseased human tissues.
先天淋巴细胞 (ILC) 在调节小鼠的免疫、炎症和组织稳态方面发挥着关键作用。然而，由于无法获得非病变的人类组织，人们难以对人类的解剖学上不同的 ILC 进行分析。通过对来自先前健康的人类器官供体的淋巴样、黏膜和代谢组织进行流式细胞术和转录分析，我们在此提供了一个人类 ILC 异质性在多个解剖部位的图谱。与小鼠不同，人类 ILC 不太严格地局限于特定组织，并且组织定位以依赖于亚群的方式选择性地影响 ILC 的分布。组织特异性差异在 ILC1 群体中尤为明显，其在肥胖或衰老时的分布明显改变。此外，在淋巴样和黏膜部位之间，ILC1 群体的异质性程度也有很大差异。总之，这些分析全面描述了调节非病变人类组织中 ILC 解剖分布、亚群异质性和功能潜力的时空动态。
