Sex differences in inflammation, redox biology, mitochondria and autoimmunity
Open accessAbstract
Autoimmune diseases are characterized by circulating antibodies and immune complexes directed against self-tissues that result in both systemic and organ-specific inflammation and pathology. Most autoimmune diseases occur more often in women than men. One exception is myocarditis, which is an inflammation of the myocardium that is typically caused by viral infections. Sex differences in the immune response and the role of the sex hormones estrogen and testosterone are well established based on animal models of autoimmune viral myocarditis as well as in mitochondrial function leading to reactive oxygen species production. RNA viruses like coxsackievirus B3, the primary cause of myocarditis in the US, activate the inflammasome through mitochondrial antiviral signaling protein located on the mitochondrial outer membrane. Toll-like receptor 4 and the inflammasome are the primary signaling pathways that increase inflammation during myocarditis, which is increased by testosterone. This review describes what is known about sex differences in inflammation, redox biology and mitochondrial function in the male-dominant autoimmune disease myocarditis and highlights gaps in the literature and future directions.
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Upregulation of complement and TLRs including TLR4 are key immune pathways that promote myocarditis in the autoimmune-CVB3 animal model.
“We have published previously that upregulation of complement and TLRs including TLR4 are key immune pathways that promote myocarditis in the autoimmune-CVB3 animal model”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [63]
The section on myocarditis in autoimmune disease (page unavailable) reports elevated TLR4 expression in male mice with autoimmune CVB3 myocarditis and less myocarditis in TLR4-deficient mice, supporting a role for TLR4 in promoting disease. Our copy does not identify complement upregulation, or upregulation of TLRs beyond TLR4, as pathways promoting myocarditis in that model. (LLM, conf=0.86)
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- Authors
- Di Florio, D. N., Sin, J., Coronado, M. J., Atwal, P. S., & Fairweather, D.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Whitman College (US)
- Mayo Clinic (US)
- Corresponding author
- Fairweather, DeLisa
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 31
- Pages
- 101482
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC7212489
- OpenAlex
- W3010344840
- Cited by
- 185
- References
- 164
- Citations by year
- 2026: 30 · 2025: 24 · 2024: 26 · 2023: 44 · 2022: 29 · 2021: 19 · 2020: 12 · 2019: 1
- FWCI
- 4.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Mayo Clinic
- National Institutes of Health (R21 AI145356, R21 AI152318, TL1 TR002380)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- sex differences, autoimmune myocarditis, viral myocarditis, coxsackievirus B3, inflammasome, TLR4, reactive oxygen species, mitochondrial function, estrogen, testosterone, inflammation, autoimmunity
- MeSH terms
- Animals, Autoimmune Diseases, Biology, Disease Models, Animal, Female, Humans, Inflammation, Male, Mitochondria, Myocardium, Oxidation-Reduction, Sex Characteristics, Autoimmunity
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