# Identification of lncRNAs in peripheral blood mononuclear cells associated with sepsis immunosuppression based on weighted gene co-expression network analysis

## TL;DR

This study identifies lncRNAs and their associated pathways in blood cells that are linked to immunosuppression in sepsis, offering new diagnostic and therapeutic possibilities.

## Contribution

The study identifies novel lncRNA-regulated pathways in sepsis-induced immunosuppression using WGCNA and experimental validation.

## Key findings

- A sepsis-associated module containing 4,193 lncRNAs was identified.
- Three immunosuppression-related pathways were linked to sepsis: Th17 cell differentiation, cytokine–cytokine receptor interactions, and cancer-related proteoglycan signaling.
- Three central genes (SLFN12, ICOS, IKZF2) and their linked lncRNAs were found to be significantly downregulated in sepsis patients.

## Abstract

Sepsis-induced immunosuppression involves complex molecular mechanisms, including dysregulated long noncoding RNAs (lncRNAs), which remain poorly understood.

We aimed to identify immunosuppression-related lncRNAs and their functional pathways in sepsis. Methods: Using weighted gene coexpression network analysis (WGCNA), we analyzed lncRNA profiles from peripheral blood mononuclear cells (PBMCs) of three sepsis patients and three healthy controls. Key modules linked to immunosuppression were validated via RT-PCR and external datasets. Pathway enrichment and protein interaction networks were employed to prioritize mechanisms.

A sepsis-associated module containing 4,193 lncRNAs revealed three immunosuppression-related pathways: Th17 cell differentiation, cytokine–cytokine receptor interactions, and cancer-related proteoglycan signaling. Protein–protein interaction networks identified three central genes (SLFN12, ICOS, IKZF2) and their linked lncRNAs (ENSG00000267074, lnc-ICOSLG-1, lnc-IKZF2-7), all significantly downregulated in sepsis patients.

Our findings highlight novel lncRNA-regulated pathways in sepsis-induced immunosuppression, providing potential targets for improved diagnosis and therapy.

The online version contains supplementary material available at 10.1186/s41065-025-00400-z.