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Heterogeneity of NKp46+ ILC in skin pre-cancerous lesions

ABSTRACT: The family of innate lymphoid cells (ILC) comprises the well-described conventional cytotoxic natural killer cells (NK cells) that patrol lymphoid and non-lymphoid organs to discriminate and eliminate stressed cells (i.e. infected and tumor cells) as well as other ILC subsets that are mainly located in epithelial tissue. How a tumor influences the phenotype and function of those ILC populations at different stages of carcinogenesis is of growing interest. We performed functional and transcriptomic analyses of purified NKp46+ innate lymphoid cells (ILC) from skins, cutaneous lesions and lymph nodes of mice subjected to chemically-induced skin carcinogenesis. We showed that isolated papilloma-derived NKp46+ ILC showed the most divergent gene expression profile compared to their surrounding skin and tumor counterpart. our study indicates that NKp46+ ILC isolated at pre-cancerous stage were enriched in ILC1 subset with less cytotoxic potential than NKp46+ ILC from tumors. These findings revealed a so far unappreciated behavior of NKp46+ ILC at different stages of skin carcinogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE84027 | GEO | 2021/05/08

REPOSITORIES: GEO

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Project description:Understanding Natural Killer (NK) cell anatomical distribution is key to dissect the role of these unconventional lymphocytes in physiological and disease conditions. In mouse, NK cells have been detected in various lymphoid and non-lymphoid organs, while in humans the current knowledge of NK cell distribution at steady state is mainly restricted to lymphoid tissues. The translation to humans of findings obtained in mice is facilitated by the identification of NK cell markers conserved between these two species. The Natural Cytotoxicity Receptor (NCR) NKp46 is a marker of the NK cell lineage evolutionary conserved in mammals. In mice, NKp46 is also present on rare T cell subsets and on a subset of gut Innate Lymphoid Cells (ILCs) expressing the retinoic acid receptor-related orphan receptor gammat (RORgammat) transcription factor. Here, we documented the distribution and the phenotype of human NKp46+ cells in lymphoid and non-lymphoid tissues isolated from healthy donors. Human NKp46+ cells were found in splenic red pulp, in lymph nodes, in lungs and gut lamina propria, thus mirroring mouse NKp46+ cell distribution. We identified a novel cell subset of CD56dimNKp46low cells that includes RORgammat+ILCs with a lineage-CD94-CD117brightCD127bright phenotype.We also included data regarding the genome-wide transcriptional profiles of human healthy colonic NK cells and RORgammat+ILCs.The use of NKp46 thus contributes to establish the basis for analyzing quantitative and qualitative changes of NK cell and ILC subsets in human diseases. Human colonic CD56-NKp46lowCD117brightCD127bright cells = LTi cells and CD56+NKp46+CD117-CD127- cells =NK cells were isolated from macroscopically unaffected areas of colon of patients with colon cancer. Indicated populations were sorted and immediately lysed in RLT buffer supplemented with 10% beta-mercaptoethanol (Quiagen, France). Lysates of three distinct donors were pooled and RNA was isolated by using RNAeasy Microkit (Quiagen, France). Duplicates were performed for each cell type. cRNA were obtained after double amplification using the MessageAmp II aRNA Amplification Kit (Ambion, France). cRNA were then hybridized on Human Genome HG_U133 +2.0 Affymetrix chips. Chip images were generated using Affymetrix AGCC 3.2 software, then expression data were extracted and normalized using Affymetrix Expression console 1.1 with the algorithm RMA. Data obtained were expressed as log2.

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Heterogeneity of NKp46+ ILC in skin pre-cancerous lesions

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