# Advances in the study of low-density neutrophils in rheumatic diseases

## TL;DR

Low-density neutrophils (LDNs) are linked to rheumatic diseases and may offer new therapeutic approaches due to their role in inflammation and disease progression.

## Contribution

The paper reviews the biological characteristics and therapeutic potential of LDNs in rheumatic diseases.

## Key findings

- LDNs are abnormally expanded in rheumatic diseases and correlate with disease activity.
- LDNs contribute to disease through NETs, cytokines, and immune regulation.
- Targeting LDNs or their pathways could lead to precision therapies for rheumatic diseases.

## Abstract

Rheumatic diseases are characterized by immune dysfunction, chronic inflammation and tissue damage, in which neutrophils play a pivotal role. As a heterogeneous subset of neutrophils, low-density neutrophils (LDNs) are present at extremely low levels in healthy individuals, whereas they are abnormally expanded in patients with rheumatic diseases and closely correlated with disease activity. This review summarizes the biological characteristics of LDNs, as well as their roles and potential therapeutic values in various rheumatic diseases. These cells exhibit a dual origin with distinct phenotypic and functional features and exert their pathogenic effects primarily through the release of neutrophil extracellular traps (NETs) and pro-inflammatory cytokines, as well as their involvement in the immune regulatory network. LDNs are implicated in the pathogenesis of multiple rheumatic diseases. Targeting LDNs or their key pathogenic pathways may provide novel insights into the precision therapy of rheumatic diseases. Further investigations into the subpopulations and underlying mechanisms of action of LDNs are therefore warranted to advance the development of targeted therapeutic strategies for these diseases.