Abstract
Phenotypic definition of helper ILC1 and NK cells is problematic due to overlapping markers. Recently we showed the identification of cytotoxic ILC3s characterized by expression of CD94. Here we analyse CD127+ ILCs and NK cells in intestinal lamina propria from healthy donors and Crohn’s disease patients and identify two populations of CD127+CD94+ ILCs, designated population A and B, that can be distinguished on the expression of CD117, CD18 and cytotoxic molecules. Population B expresses granulysin, a cytotoxic molecule linked to bacterial lysis and/or chemotaxis of monocytes. Granulysin protein is secreted by population B cells upon stimulation with IL-15. Activation of population B in the presence of TGF-β strongly reduces the expression of cytotoxic effector molecules of population B. Strikingly, samples from individuals that suffer from active Crohn’s disease display enhanced frequencies of granulysin-expressing effector CD127+CD94+ ILCs in comparison to controls. Thus this study identifies group 1 ILC populations which accumulate in inflamed intestinal tissue of Crohn’s disease patients and may play a role in the pathology of the disease.
Highlights
Phenotypic definition of helper ILC1 and NK cells is problematic due to overlapping markers
Cluster 1 and cluster 7 express genes that are associated with ILC3s and ILC2s, such as IL7R and low RORC levels and are enriched for genes that are involved in transcriptional regulation and cytokine production (FOS JUNB/D, LIF), regulation of inflammation (TNFAIP3) and wound repair (AREG) (Fig. S2a)
Analysis of human intestinal NK/Innate lymphoid cells (ILCs) pool by single-cell RNA sequencing ILCs and NK cells, sorted by flow cytometry, reveals the existence of conventional NK cells, helper ILC clusters, a cluster resembling Lymphoid-Tissue inducer (LTi) cells, and two additional ILC clusters that are characterized by co-expression of CD127 and CD94
Summary
Phenotypic definition of helper ILC1 and NK cells is problematic due to overlapping markers. Using scRNAseq we identified CD127+CD94+ ILC1s that highly expressed granulysin, a cytotoxic molecule that is linked to bacterial lysis and/or chemotaxis of monocytes[12,13,14,15,16] These cells were isolated using antibodies against cell surface molecules identified with scRNAseq and further characterization confirmed that these cells highly express granulysin protein, indicating they are in an activated state in vivo. We found that these ILC1s were present in adult but not in fetal intestinal tissue and are dramatically enhanced in frequency in patients that suffer from Crohn’s disease as compared to non-inflamed intestinal tissue
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