Neutrophils isolated from systemic lupus erythematosus patients exhibit a distinct functional phenotype.

Autor:	Jog NR; Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States., Wagner CA; Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States., Aberle T; Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States., Chakravarty EF; Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States., Arriens C; Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States., Guthridge JM; Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States., James JA; Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States.; Departments of Medicine and Pathology, University of Oklahoma Health Science Center, Oklahoma City, OK, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Mar 08; Vol. 15, pp. 1339250. Date of Electronic Publication: 2024 Mar 08 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1339250
Abstrakt:	Neutrophil dysregulation, particularly of a low-density subset, is associated with systemic lupus erythematosus (SLE); however, the exact role of normal-density neutrophils in SLE remains unknown. This study compares activation and functional phenotypes of neutrophils from SLE patients and healthy controls to determine potential contributions to SLE pathogenesis. Surface activation markers and release of neutrophil extracellular traps (NETs), granule proteins, and cytokines/chemokines were measured in resting and stimulated neutrophils from SLE patients (n=19) and healthy controls (n=10). Select miRNA and mRNA involved in neutrophil development and function were also measured. Resting SLE neutrophils exhibited fewer activation markers compared to control neutrophils, and activation markers were associated with different plasma cytokines/chemokines in SLE patients compared to healthy controls. However, activation markers increased similarly in SLE and control neutrophils following stimulation with a TLR7/8 agonist, neutrophil growth factors, and bacterial mimic. At the resting state, SLE neutrophils produced significantly more CXCL10 (IP-10), with trends toward other increased cytokines/chemokines. Following stimulation, SLE neutrophils produced fewer NETs and proinflammatory cytokines compared to control neutrophils but more MMP-8. In addition, SLE neutrophils expressed less miR130a, miR132, miR27a, and miR223. In conclusion, SLE neutrophils exhibit distinct functional responses compared to control neutrophils. These functional differences may result from differential gene expression via miRNAs. Furthermore, the differences in functional phenotype of SLE neutrophils suggest that they may contribute to SLE differently dependent on the inflammatory milieu. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Jog, Wagner, Aberle, Chakravarty, Arriens, Guthridge and James.)
Databáze:	MEDLINE
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