Foundry120 atlas

CD45RA+CD62L- ILCs represent a quiescent local reservoir for the generation of mature ILC in human tissues

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Dataset overview

Participants None
Samples None
Reuse readiness 4.6/10 evidence-backed score

CD45RA<sup>+</sup>CD62L<sup>-</sup> ILCs in human tissues represent a quiescent local reservoir for the generation of differentiated ILCs.

Abstract

Innate lymphoid cells (ILCs) are highly plastic and predominantly mucosal tissue-resident cells that contribute to both homeostasis and inflammation depending on the microenvironment. The discovery of naïve-like ILCs suggests an ILC differentiation process that is akin to naïve T cell differentiation. Delineating the mechanisms that underlie ILC differentiation in tissues is crucial for understanding ILC biology in health and disease. Here, we showed that tonsillar ILCs expressing CD45RA lacked proliferative activity, indicative of cellular quiescence. CD62L distinguished two subsets of CD45RA<sup>+</sup> ILCs. CD45RA<sup>+</sup>CD62L<sup>+</sup> ILCs (CD62L<sup>+</sup> ILCs) resembled circulating naïve ILCs because they lacked the transcriptional, metabolic, epigenetic, and cytokine production signatures of differentiated ILCs. CD45RA<sup>+</sup>CD62L<sup>-</sup> ILCs (CD62L<sup>-</sup> ILCs) were epigenetically similar to CD62L<sup>+</sup> ILCs but showed a transcriptional, metabolic, and cytokine production signature that was more akin to differentiated ILCs. CD62L<sup>+</sup> and CD62L<sup>-</sup> ILCs contained uni- and multipotent precursors of ILC1s/NK cells and ILC3s. Differentiation of CD62L<sup>+</sup> and CD62L<sup>-</sup> ILCs led to metabolic reprogramming including up-regulation of genes associated with glycolysis, which was needed for their effector functions after differentiation. CD62L<sup>-</sup> ILCs with preferential differentiation capacity toward IL-22-producing ILC3s accumulated in the inflamed mucosa of patients with inflammatory bowel disease. These data suggested distinct differentiation potential of CD62L<sup>+</sup> and CD62L<sup>-</sup> ILCs between tissue microenvironments and identified that manipulation of these cells is a possible approach to restore tissue-immune homeostasis.

Study facts

Organism
Homo sapiens
Platform
Illumina NextSeq 500
Age group
mixed
Disease groups
—
Anatomical sites
large intestine

Data availability

  • Raw counts

File types BEDTXT

Files and samples

Strengths & limitations for reuse

Strengths

  • Raw counts are advertised

Limitations

  • Not documented: processed matrices are advertised
  • Not documented: cell metadata are advertised
  • Not documented: participant counts are documented
Extraction evidence & provenance

Each extracted field is shown with the source excerpt and location used to resolve it.

Assay

FieldValueEvidence
assay.assay_type Smart-seq2 single-cell RNA-seq
Smart-seq2 single cell data downstream analysis were perfored using R package Seurat v3.2.3.

Section data_processing, offset —

assay.library_chemistry SMART-Seq2
Samples were prepared using the SMART-Seq2 platform according to manufacturer’s instructions.

Section extract_protocol, offset —

assay.platform Illumina NextSeq 500
Illumina NextSeq 500

Section instrument_model, offset —

assay.reference_genome GRCh37.87 (hg19)
Trimmed reads were mapped to the Homo sapiens genome (GRCh37.87 assembly) using STAR (v2.5.3a) mapper

Section data_processing, offset —

assay.sequencing_type scrna_seq
K22_GNI3_P188 [scRNA-seq]

Section samples, offset —

Cohort

FieldValueEvidence
cohort.age_group mixed from source
GEO age characteristics: 5; 6; 25; 13; 5; 6; 25; 13; 5; 6; 25; 13; 5; 6; 25; 13; 5; 6; 25; 13; 5; 6; 25; 13; 14; 12; 29; 17; 13; 35; 12; 29; 17; 13; 35; 12; 29; 17; 13; 35; 12; 29; 17; 14; 12; 29; 17; 14; 12; 29; 17; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57; 57;

Section GEO family SOFT, offset —

cohort.crohns_disease_participants 3
inflamed biopsies from the large intestine were obtained from three Crohn’s disease patients

Section extract_protocol, offset —

cohort.disease_activity_metadata_available True from source
GEO sample characteristics document disease activity

Section GEO family SOFT, offset —

cohort.non_ibd_controls 3
Non-inflamed biopsies from the large intestine were obtained from three tumor-screening patients

Section extract_protocol, offset —

Data_Assets

FieldValueEvidence
data_assets.raw_counts True
GSE176367_Gene_Raw_Count_Single_Cell_RNA-seq_Smart-seq2.txt.gz

Section series_supplementary_file, offset —

data_assets.raw_reads False
due to the privacy of patients, the raw data is not provided

Section series_overall_design, offset —

Specimens

FieldValueEvidence
specimens.anatomical_sites ['large intestine']
Non-inflamed biopsies from the large intestine

Section extract_protocol, offset —

specimens.specimen_type biopsy
Non-inflamed biopsies from the large intestine were obtained from three tumor-screening patients

Section extract_protocol, offset —