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What's wrong with neutrophils in lupus?
Chang-Youh Tsai1, Ko-Jen Li2, Song-Chou Hsieh2
1Division of Allergy, Immunology and Rheumatology, Taipei Veterans General Hospital, and National Yang-Ming University School of Medicine, Taipei, Taiwan.
Clinical and Experimental Rheumatology
|December 18, 2018
Summary
Polymorphonuclear neutrophils (PMNs) have novel immune functions beyond pathogen defense. Dysfunctional PMNs and autoantibodies contribute to systemic lupus erythematosus (SLE) pathogenesis.
Area of Science:
- Immunology
- Cell Biology
- Autoimmunity
Background:
- Polymorphonuclear neutrophils (PMNs) are key immune cells with diverse functions beyond phagocytosis.
- Systemic lupus erythematosus (SLE) is an autoimmune disease marked by widespread immune system dysfunction.
- PMNs exhibit previously unrecognized roles in cytotoxicity, cell signaling, and extracellular trap formation.
Purpose of the Study:
- To review the multifaceted functions of PMNs.
- To explore the immune dysfunctions observed in SLE patients.
- To elucidate the role of aberrant PMN functions in SLE pathogenesis.
Main Methods:
- Literature review of PMN functions and SLE pathology.
- Analysis of PMN abnormalities in SLE patients, including cytokine expression and metabolism.
- Investigation of autoantibody effects on PMN function.
Main Results:
- PMNs perform functions including cytotoxicity, cytokine release, NET formation, and trogocytosis.
- SLE patients exhibit immune dysfunctions such as increased IFN-α, aberrant cytokine profiles, and impaired NET clearance.
- SLE-derived PMNs show abnormal cytokine expression, defective glucose metabolism, and increased mitochondrial DNA heteroplasmy.
- Autoantibodies from SLE sera impair PMN functions.
Conclusions:
- Disrupted PMN functions, influenced by autoantibodies, are implicated in SLE pathogenesis.
- Understanding these PMN abnormalities offers insights into SLE mechanisms.
- Further research into PMN roles can guide SLE therapeutic strategies.