REVIEW article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
This article is part of the Research TopicAdvances in pathogenetic mechanisms of immune-mediated rheumatic diseases with forthcoming therapeutic implicationsView all articles
Advances in the study of low-density neutrophils in rheumatic diseases
Provisionally accepted
- 1Anhui University of Chinese Medicine, Hefei, China
- 2Anhui University of Chinese Medicine School of Pharmacy, Hefei, China
- 3Anhui Province Key Laboratory of Research & Development of Chinese Medicine, Hefei, China
- 4University of Science and Technology of China, Hefei, China
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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.
Keywords: Autoimmunity, low-density neutrophils, neutrophil extracellular traps, Rheumatic disease, Systemic lupuserythematosus
Received: 16 Nov 2025; Accepted: 16 Feb 2026.
Copyright: © 2026 Yin, Wang, Cai, Zhang and Jia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaoyi Jia
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