Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency

Abstract

Animal models have highlighted the importance of innate lymphoid cells (ILCs) in multiple immune responses. However, technical limitations have hampered adequate characterization of ILCs in humans. Here, we used mass cytometry including a broad range of surface markers and transcription factors to accurately identify and profile ILCs across healthy and inflamed tissue types. High dimensional analysis allowed for clear phenotypic delineation of ILC2 and ILC3 subsets. We were not able to detect ILC1 cells in any of the tissues assessed, however, we identified intra-epithelial (ie)ILC1-like cells that represent a broader category of NK cells in mucosal and non-mucosal pathological tissues. In addition, we have revealed the expression of phenotypic molecules that have not been previously described for ILCs. Our analysis shows that human ILCs are highly heterogeneous cell types between individuals and tissues. It also provides a global, comprehensive, and detailed description of ILC heterogeneity in humans across patients and tissues.

Changes in bone marrow innate lymphoid cell subsets in monoclonal gammopathy: target for IMiD therapy

“…19,20 To address this in the setting of human marrow, we analyzed transcriptional profiles of sorted CD3 -CD56 1 NK cells and ILC1 from healthy bone marrow using single-cell RNA sequencing (GEO submission, GSE105216 (Figure 2A-C; supplemental Figure 2). These data demonstrate that ILC1 identified in our studies is distinct from NK cells.…”

Interleukins 12 and 15 induce cytotoxicity and early NK-cell differentiation in type 3 innate lymphoid cells

“…The findings that human NK cells can be derived from RORgtexpressing precursors 18,19 and the controversial existence of an ILC1 population distinct from NK cells in humans 11 suggest fundamental species differences in ILC biology [25][26][27] and the need for a better experimental model to study human ILC biology. To that end, we characterized ILCs, specifically ILC3s and NK cells, in NOD-scid Il2rg null mice engrafted with human CD34 1 hematopoietic progenitor cells, denoted as huNSG mice (human reconstitution shown in supplemental Figure 1).…”

Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications

“…12 The most prevalent ILC population in human skin is the ILC2. 3 As skin ILC2s express high levels of amphiregulin, they are implicated in tissue homeostasis and repair. 73 This is supported by increased ILC2 numbers in healing cutaneous wounds.…”