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

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.