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Persistent dysfunction of Th17 cells in people with HIV on ART and in elite controllers

GSE252771 Homo sapiens (human) RNA-seq (gene expression) 28 samples Submitted 2024/06/30 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 28 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
28 samples
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Altered memory CCR6(+) Th17-polarised T-cell function and biology in people with HIV under successful antiretroviral therapy and HIV elite controllersEBioMedicine · 2024
Summary (written by the submitters)
Th17 cells are rapidly depleted during HIV infection and their frequencies and functions are not fully restored by antiretroviral therapy (ART). In addition, Th17 cells contribute to viral persistence during ART. However, molecular mechanisms underlying these observations remain understudied. MemCCR6+ cells from STs vs. HDs showed alterations in the NOTCH and TGF-β1/smad2-3 pathways, indicative of impairments in their differentiation and stability.
Read the full summary ↓
Consistently, the RORγt/C2 repressor NR1D1 was upregulated, while Semaphorin 4D, a RORγt/C2 inducer, was decreased in MemCCR6+ cells from STs vs. HDs. Frequencies of Th17 and Th1/Th17 cells within total MemCCR6+ cells were lower in STs and ECs compared to HD individuals, and expressed higher levels of activation and senescence/exhaustion markers. As a result, MemCCR6+ cells from STs produced less IL-17A/F, IL-22, and IFN-γ in vitro compared to HDs. Downregulation of HIV restriction factors (SERINC3, KLF3, and RNF125) and HIV inhibitors (tetraspanins), along with increased expression of MRE11 in MemCCR6+ cells from ST individuals supported higher susceptibility/permissiveness to HIV infection. MemCCR6+ cells from STs and ECs had lower TFAP4 expression and increased expression of EED and TP53BP1 vs. HDs, which is associated to HIV persistence. Markers of DNA damage/modification were elevated in STs and ECs compared to HDs, including NASP, RPA2, H2AX, PARP, and DNA methylases DNMT1/DNMT3A. Similar to the ST group, MemCCR6+ cells in ECs showed decreased expression of Semaphorin 4D and Notch1, along with higher expression of NR1D1 compared to HD donors. Despite successful ART, the transcriptional signature of MemCCR6+ cells revealed impaired differentiation, stability, functions, DNA damage/modifications, and higher susceptibility to HIV infection and viral persistence.
Published in
Altered memory CCR6(+) Th17-polarised T-cell function and biology in people with HIV under successful antiretroviral therapy and HIV elite controllers
Yero A, Goulet JP, Shi T et al. · EBioMedicine 2024 · PMID 39178742 · doi:10.1016/j.ebiom.2024.105274
This dataset
Open GSE252771 in finder → Find more human RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE252771_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1062421 and SRA study SRP482577. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39178742) ↗
Samples in this study

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