Low-Density Neutrophils in Systemic Lupus Erythematosus

Area of Science:

• Immunology
• Rheumatology
• Cell Biology

Background:

• Systemic lupus erythematosus (SLE) is characterized by increased immature neutrophils.
• Low-density neutrophils (LDNs) are found in the peripheral blood mononuclear cell fraction.
• LDNs play emerging roles in immune responses beyond antimicrobial functions.

Purpose of the Study:

• To review the origin, nature, and biologic roles of LDNs in SLE.
• To elucidate the heterogeneous composition and functions of LDNs in SLE.
• To update the literature on LDN contributions to SLE immunopathogenesis and end-organ damage.

Main Methods:

• Literature review of studies on LDNs in SLE.
• Analysis of multiomic approaches to understand LDN phenotype and function.
• Examination of LDN polarization based on CD10 expression (mature vs. immature).

Main Results:

• LDNs in SLE are heterogeneous, comprising mature and immature neutrophils.
• LDNs contribute to inflammation and tissue damage by secreting type I interferon (IFN).
• LDNs form neutrophil extracellular traps (NETs) exposing autoantigens and oxidized mitochondrial DNA, promoting autoantibody production and IFN signaling.

Conclusions:

• LDNs are key players in SLE pathogenesis, contributing to inflammation and autoantibody production.
• The functional polarization of LDNs (CD10+ vs. CD10-) is critical in SLE.
• Further research into LDNs is vital for understanding and potentially treating SLE.