Omega-3 Polyunsaturated Fatty Acid Intervention Against Established Autoimmunity in a Murine Model of Toxicant-Triggered Lupus

Autor: James J. Pestka, Peyman Akbari, Kathryn A. Wierenga, Melissa A. Bates, Kristen. N. Gilley, James G. Wagner, Ryan P. Lewandowski, Lichchavi D. Rajasinghe, Preeti S. Chauhan, Adam L. Lock, Quan-Zhen Li, Jack R. Harkema
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
lcsh:Immunologic diseases. Allergy
medicine.medical_specialty
ectopic lymphoid structure
Immunology
medicine.disease_cause
Autoimmunity
03 medical and health sciences
chemistry.chemical_compound
Mice
NZBWF1
0302 clinical medicine
ω-3 polyunsaturated fatty acid
systemic lupus erythematosus
Internal medicine
Fatty Acids
Omega-3
medicine
Animals
Humans
Lupus Erythematosus
Systemic
Immunology and Allergy
Original Research
chemistry.chemical_classification
Inhalation Exposure
Systemic lupus erythematosus
business.industry
Autoantibody
Glomerulonephritis
docosahexaenoic acid
Fish oil
medicine.disease
Silicon Dioxide
Occupational Diseases
Disease Models
Animal
030104 developmental biology
Endocrinology
chemistry
Docosahexaenoic acid
silica
030220 oncology & carcinogenesis
Dietary Supplements
Disease Progression
Arachidonic acid
Female
business
lcsh:RC581-607
glomerulonephritis
autoantibody
Polyunsaturated fatty acid
Zdroj: Frontiers in Immunology, Vol 12 (2021)
Frontiers in Immunology
ISSN: 1664-3224
DOI: 10.3389/fimmu.2021.653464
Popis: Workplace exposure to respirable crystalline silica dust (cSiO2) has been etiologically linked to the development of lupus and other human autoimmune diseases. Lupus triggering can be recapitulated in female NZBWF1 mice by four weekly intranasal instillations with 1 mg cSiO2. This elicits inflammatory/autoimmune gene expression and ectopic lymphoid structure (ELS) development in the lung within 1 week, ultimately driving early onset of systemic autoimmunity and glomerulonephritis. Intriguingly, dietary supplementation with docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid (PUFA) found in fish oil, beginning 2 week prior to cSiO2 challenge, prevented inflammation and autoimmune flaring in this novel model. However, it is not yet known how ω-3 PUFA intervention influences established autoimmunity in this murine model of toxicant-triggered lupus. Here we tested the hypothesis that DHA intervention after cSiO2-initiated intrapulmonary autoimmunity will suppress lupus progression in the NZBWF1 mouse. Six-week old NZWBF1 female mice were fed purified isocaloric diet for 2 weeks and then intranasally instilled with 1 mg cSiO2 or saline vehicle weekly for 4 consecutive weeks. One week after the final instillation, which marks onset of ELS formation, mice were fed diets supplemented with 0, 4, or 10 g/kg DHA. One cohort of mice (n = 8/group) was terminated 13 weeks after the last cSiO2 instillation and assessed for autoimmune hallmarks. A second cohort of mice (n = 8/group) remained on experimental diets and was monitored for proteinuria and moribund criteria to ascertain progression of glomerulonephritis and survival, respectively. DHA consumption dose-dependently increased ω-3 PUFA content in the plasma, lung, and kidney at the expense of the ω-6 PUFA arachidonic acid. Dietary intervention with high but not low DHA after cSiO2 treatment suppressed or delayed: (i) recruitment of T cells and B cells to the lung, (ii) development of pulmonary ELS, (iii) elevation of a wide spectrum of plasma autoantibodies associated with lupus and other autoimmune diseases, (iv) initiation and progression of glomerulonephritis, and (v) onset of the moribund state. Taken together, these preclinical findings suggest that DHA supplementation at a human caloric equivalent of 5 g/d was an effective therapeutic regimen for slowing progression of established autoimmunity triggered by the environmental toxicant cSiO2.
Databáze: OpenAIRE
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