GSE133426

Human memory Th17 cell populations change into anti-inflammatory cells with regulatory capacity upon exposure to active Vitamin D

Whole-study status Not suitable

Dataset does not meet the current suitability threshold.

Whole-study downloads — these do not apply your sample requirements.

Selected cohort requirements

Samples meeting selected requirements: 0 cases / 0 controls

View matching samples

3 case / 3 control samples elsewhere in the study have incomplete or conflicting evidence; they are not included above

Patient pairs verified in indexed sample metadata: 0

A case/control comparison meeting these requirements is not confirmed.

Counts describe samples, not independent patients. Pair verification uses explicit subject identifiers in indexed sample metadata. Zero verified pairs does not establish that the study is unpaired; reported matched-normal design alone is insufficient.

Source: GEO
Assay: microarray
Organism: Homo sapiens
Whole-study samples: 6 samples
Specimen: Unclear specimen/source
Reported/interpreted study design: Treatment vs control Design classification does not establish patient pairs.

Comparison type: Tumor vs normal
Contributors: Dankers W, Davelaar N, van Hamburg JP, van de Peppel J, Colin EM, Lubberts E
Contact name: Jeroen van de Peppel
Submission date: 2019-06-27
Last update: 2019-08-16
Organization: ErasmusMC
Department: Not available
Public date: 2019-06-28
Experiment types: Expression profiling by array
Platforms: GPL10558 Illumina HumanHT-12 V4.0 expression beadchip
Series type: Series
SubSeries: Not available
BioProject: PRJNA551440

Summary

Autoimmune diseases are characterized by an aberrantly activated immune system, resulting in tissue damage and functional disability in patients. An important therapeutic goal is to restore the deregulated immunological balance between pro- and anti-inflammatory T cells. This imbalance is illustrated by elevated levels and activity of memory Th17 cell populations, such as Th17, Th1/Th17 and Th17.1 cells, in various autoimmune diseases. These cells are characterized by the chemokine receptor CCR6, RORC expression and production of IL-17A, IFNγ and TNFα. Using rheumatoid arthritis (RA) as a model autoimmune disease, we here demonstrate that pro-inflammatory memory CCR6+ Th cells can switch into anti-inflammatory cells with regulatory capacity using the active vitamin D metabolite 1,25(OH)2D3. Memory CCR6+ Th cells, excluding Tregs, were sorted from healthy controls or treatment-naïve patients with early rheumatoid arthritis (RA) and cultured with or without 1,25(OH)2D3. Treatment with 1,25(OH)2D3 inhibited pro-inflammatory cytokines such as IL-17A, IL-17F, IL-22 and IFNγ in memory CCR6+ Th cells from both healthy controls and RA patients. This was accompanied by induction of anti-inflammatory factors, including IL-10 and CTLA4. Interestingly, these formerly pathogenic cells suppressed proliferation of autologous CD3+ T cells similar to classical Tregs. Importantly, the modulated memory cells still migrated towards the site of inflammation, modelled by RA synovial fluid, and retained their suppressive capacity in this environment. These data show the potential to reset the pathogenic profile of human memory Th cells into non-pathogenic cells with regulatory capacity.

Overall design

CCR6 positive Th17 cells from 3 independent treatment naive early RA patients were stimulated with anti-CD3/anti-CD28 and exposed with or without Vitamin D for 72 hours.

Source Evidence

4 sources

Source	Contribution	Status
GEO	Original dataset metadata, sample metadata, source links, and GEO data availability flags. Sample records 6 GSM samples	Primary source
recount3	Planned trusted source for processed count availability.	No match found
Expression Atlas	Planned source for curated expression experiment links.	No match found
PubMed	Primary GEO citations and related PubMed articles that mention this dataset. 1 linked publication 1 DOI Primary publication Human Memory Th17 Cell Populations Change Into Anti-inflammatory Cells With Regulatory Capacity Upon Exposure to Active Vitamin D. Frontiers in immunology, 2019 PubMed DOI	Available

Metadata Quality Components

Persisted metadata quality

100 pts

Clarity: 100%
Weight: 100 pts

Sample source clarity: All samples have source metadata and clear GSE/GSM accessions. Group clarity: Rule-based grouping found both case and control samples. Disease clarity: Disease or condition metadata normalized. Tissue clarity: Anatomical source metadata normalized. Treatment clarity: Treatment status metadata normalized where treatment is part of the comparison. Replicate clarity: No pooled sample or technical replicate flags detected. Data availability clarity: Dataset-level processed or raw data availability is explicit.

Analysis Readiness

Ready after review

97% DE readiness

Contrast completeness

25/25 pts

Both case and control groups are present in the proposed grouping.

Minimum group size

20/20 pts

Each contrast group has at least 2 samples.

Processed data availability

20/20 pts

Processed data is marked available in the GEO index.

Sample decision clarity

15/15 pts

All samples are assigned to a case or control group.

Blocking warnings

7/10 pts

Warnings are present, but none are critical blockers.

Metadata normalization

10/10 pts

Metadata quality is high enough to support downstream handoff.

Blockers

No readiness blockers detected.

Next Steps

Verify the proposed sample assignments and case-versus-control comparison against the GEO metadata before using them in DESeq2 or another differential-expression tool.
Confirm processed count files and sample identifiers match the exported metadata.

Analysis Preparation Checklist

5/6 ready

Group labels reviewed

Needs review

Siftome proposed case and control labels, but no reviewer confirmation is stored yet.

Open the sample grouping CSV and confirm group labels before analysis.

Minimum sample count met

Ready

Both groups meet the minimum of 2 samples.

Confirm whether the cohort is large enough for the intended statistical analysis.

Processed counts available

Ready

Processed data availability is marked true in the GEO index.

Verify that downloaded processed files contain usable count or expression identifiers.

Ambiguous samples handled

Ready

No review-needed or unassigned samples are present in the proposed grouping.

Review the grouping table for biologically meaningful differences that the automated checks may not detect.

Exclusion decisions recorded

Ready

No hard-excluded samples were detected by the current rules.

Record any manual exclusions in the downstream analysis notes.

Source traceability preserved

Ready

The dataset and sample accessions can be traced back to GEO.

Keep GEO accessions with exported metadata.

Bioinformatician Review

Bioinformatician review required

Ask a bioinformatician to review grouping, count availability, exclusions, and design before DE.

Assay context may require expert handling before DESeq2-style analysis.

Why This Is Ranked Here

Tumor vs normal

Not suitable Dataset does not meet the current suitability threshold.

Applied Review Decisions

No active review decisions affect this ranking.

Derived Classifications

Assay differs from search intent Microarray Search intent expects bulk RNA-seq. Assay came from Normalization rules.
Disease context Rheumatoid arthritis Disease context came from Normalization rules.
Likely case group Treated 3 samples
Likely control group Untreated 3 samples

Intent Interpretation

Downgrade or exclusion reason Comparison: Treatment vs control. Specimen: Unclear specimen/source. Comparison suitability: 0%. Derived from current-intent ranking reasons.

Ranking Facts

Supporting evidence

Interpreted disease metadata: Rheumatoid arthritis.
Processed data is available for downstream review.
External evidence: PubMed links 1 publication; 1 DOI available: PMID 31379807.
Publication context: Human Memory Th17 Cell Populations Change Into Anti-inflammatory Cells With Regulatory Capacity Upon Exposure to Active Vitamin D.. Frontiers in immunology, 2019. PMID 31379807. DOI 10.3389/fimmu.2019.01504.

Cautions

Comparison: Treatment vs control. Specimen: Unclear specimen/source. Comparison suitability: 0%.
Downgraded for tissue search because it is a treatment/control experiment.
Downgraded for tissue search because study design or specimen source is unclear.
Downgraded assay: microarray cohorts are separated from the RNA-seq intent.
Treatment/control experiment downgraded because this ranking targets tumor-vs-normal tissue comparisons.
Unclear specimen/source downgraded for patient tissue tumor-vs-normal search intent.
Missing or unclear metadata. Unclear specimen/source downgraded for patient tissue tumor-vs-normal search intent.
Overall score capped because comparison suitability is weak for the selected search intent.
Overall score capped because fewer than ten samples limit cohort confidence.
Missing or unclear metadata. Comparison - Treatment vs control. Specimen - Unclear specimen/source. Comparison suitability: 0%.
Missing or unclear metadata. Downgraded for tissue search because study design or specimen source is unclear.
Comparison suitability score is below the Phase 1 recommended threshold.

Dataset Warnings

Microarray expression context was detected; compare separately from RNA-seq cohorts.
Microarray datasets are downgraded in the patient-tissue tumor-normal intent unless secondary assays are explicitly enabled.
Patient-tissue tumor-normal intent requires tissue or biopsy source clarity.

Normalized Fields

16 fields

Field Value Source Derived by Confidence Evidence Reason

assay_type microarray GSE133426 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence microarray dataset_accession: GSE133426 dataset_title: Human memory Th17 cell populations change into anti-inflammatory cells with regulatory capacity upon exposure to active Vitamin D org... keyword match keyword match: microarray

control_type vehicle control GSM3908500 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence vehicle T_CCR6+_1588 CCR6+ T-Cells_EtOH donor 1 disease state: RA; individual: donor 1; cell type: CCR6+ T-cell; treatment: vehicle controlled vocabulary controlled vocabulary control type match: vehicle

control_type vehicle control GSM3908502 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence vehicle T_CCR6+_1614 CCR6+ T-Cells_EtOH donor 2 disease state: RA; individual: donor 2; cell type: CCR6+ T-cell; treatment: vehicle controlled vocabulary controlled vocabulary control type match: vehicle

control_type vehicle control GSM3908504 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence vehicle T_CCR6+_1811 CCR6+ T-Cells_EtOH donor 3 disease state: RA; individual: donor 3; cell type: CCR6+ T-cell; treatment: vehicle controlled vocabulary controlled vocabulary control type match: vehicle

disease rheumatoid arthritis GSE133426 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis dataset_accession: GSE133426 dataset_title: Human memory Th17 cell populations change into anti-inflammatory cells with regulatory capacity upon exposure to active Vitamin D org... controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

disease rheumatoid arthritis GSM3908500 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence ra T_CCR6+_1588 CCR6+ T-Cells_EtOH donor 1 disease state: RA; individual: donor 1; cell type: CCR6+ T-cell; treatment: vehicle controlled vocabulary controlled vocabulary disease match: ra

disease rheumatoid arthritis GSM3908501 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence ra T_CCR6+_VitD_1588 CCR6+ T-Cells_VitD donor 1 disease state: RA; individual: donor 1; cell type: CCR6+ T-cell; treatment: VitD controlled vocabulary controlled vocabulary disease match: ra

disease rheumatoid arthritis GSM3908502 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence ra T_CCR6+_1614 CCR6+ T-Cells_EtOH donor 2 disease state: RA; individual: donor 2; cell type: CCR6+ T-cell; treatment: vehicle controlled vocabulary controlled vocabulary disease match: ra

disease rheumatoid arthritis GSM3908503 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence ra T_CCR6+_VitD_1614 CCR6+ T-Cells_VitD donor 2 disease state: RA; individual: donor 2; cell type: CCR6+ T-cell; treatment: VitD controlled vocabulary controlled vocabulary disease match: ra

disease rheumatoid arthritis GSM3908504 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence ra T_CCR6+_1811 CCR6+ T-Cells_EtOH donor 3 disease state: RA; individual: donor 3; cell type: CCR6+ T-cell; treatment: vehicle controlled vocabulary controlled vocabulary disease match: ra

disease rheumatoid arthritis GSM3908505 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence ra T_CCR6+_VitD_1811 CCR6+ T-Cells_VitD donor 3 disease state: RA; individual: donor 3; cell type: CCR6+ T-cell; treatment: VitD controlled vocabulary controlled vocabulary disease match: ra

organism Homo sapiens GSE133426 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence homo sapiens dataset_accession: GSE133426 dataset_title: Human memory Th17 cell populations change into anti-inflammatory cells with regulatory capacity upon exposure to active Vitamin D org... keyword match keyword match: homo sapiens

tissue synovium GSE133426 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence synovial dataset_accession: GSE133426 dataset_title: Human memory Th17 cell populations change into anti-inflammatory cells with regulatory capacity upon exposure to active Vitamin D org... controlled vocabulary controlled vocabulary tissue match: synovial

treatment_status untreated GSM3908500 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence vehicle T_CCR6+_1588 CCR6+ T-Cells_EtOH donor 1 disease state: RA; individual: donor 1; cell type: CCR6+ T-cell; treatment: vehicle controlled vocabulary controlled vocabulary treatment status match: vehicle

treatment_status untreated GSM3908502 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence vehicle T_CCR6+_1614 CCR6+ T-Cells_EtOH donor 2 disease state: RA; individual: donor 2; cell type: CCR6+ T-cell; treatment: vehicle controlled vocabulary controlled vocabulary treatment status match: vehicle

treatment_status untreated GSM3908504 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence vehicle T_CCR6+_1811 CCR6+ T-Cells_EtOH donor 3 disease state: RA; individual: donor 3; cell type: CCR6+ T-cell; treatment: vehicle controlled vocabulary controlled vocabulary treatment status match: vehicle

Sample Group Preview

6 rows shown Show Hide

Study totals: Case 3 | Control 3 | Unassigned 0 | Excluded 0 | Ambiguous 0 6 rows shown

Group	Role	Accession	Title	Source / characteristics	Reason
Treated	Case	GSM3908501	T_CCR6+_VitD_1588	CCR6+ T-Cells_VitD donor 1 Disease state: RA; Individual: Donor 1; Cell type: CCR6+ T-cell; Treatment: VitD	Explicit characteristic comparison arm detected.
Treated	Case	GSM3908503	T_CCR6+_VitD_1614	CCR6+ T-Cells_VitD donor 2 Disease state: RA; Individual: Donor 2; Cell type: CCR6+ T-cell; Treatment: VitD	Explicit characteristic comparison arm detected.
Treated	Case	GSM3908505	T_CCR6+_VitD_1811	CCR6+ T-Cells_VitD donor 3 Disease state: RA; Individual: Donor 3; Cell type: CCR6+ T-cell; Treatment: VitD	Explicit characteristic comparison arm detected.
Untreated	Control	GSM3908500	T_CCR6+_1588	CCR6+ T-Cells_EtOH donor 1 Disease state: RA; Individual: Donor 1; Cell type: CCR6+ T-cell; Treatment: Vehicle	Treatment control marker detected.
Untreated	Control	GSM3908502	T_CCR6+_1614	CCR6+ T-Cells_EtOH donor 2 Disease state: RA; Individual: Donor 2; Cell type: CCR6+ T-cell; Treatment: Vehicle	Treatment control marker detected.
Untreated	Control	GSM3908504	T_CCR6+_1811	CCR6+ T-Cells_EtOH donor 3 Disease state: RA; Individual: Donor 3; Cell type: CCR6+ T-cell; Treatment: Vehicle	Treatment control marker detected.

Use as Discovery Cohort

External Validation Finder

Carry Siftome's disease, organism, specimen, assay, data type, and accession into a validation project. Uncertain fields remain Unknown.

Summary

Overall design

Source Evidence

Primary publication

Metadata Quality Components

Analysis Readiness

Blockers

Next Steps

Analysis Preparation Checklist

Bioinformatician Review

Why This Is Ranked Here

Applied Review Decisions

Derived Classifications

Intent Interpretation

Ranking Facts

Supporting evidence

Cautions

Dataset Warnings

Normalized Fields

Sample Group Preview

Use as Discovery Cohort