Spatial and Temporal Mapping of Human Innate Lymphoid Cells Reveals Elements of Tissue Specificity

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. •In contrast to mice, human ILCs are less strictly compartmentalized•ILC subset composition is differentially impacted by tissue localization•Tissue environment drives transcriptional heterogeneity in a subset-dependent way•ILC1 exhibit greater transcriptional heterogeneity in mucosal versus lymphoid sites Innate lymphoid cells (ILC) critically regulate tissue immunity and homeostasis in mice, but limited access to healthy human tissues has hindered efforts to profile anatomically-distinct ILCs in humans. Yudanin and colleagues provide a comprehensive map of the spatial and temporal dynamics regulating the anatomical distribution, subset heterogeneity, and functional potential of ILCs in non-diseased human tissues.