The multiple pathways to autoimmunity
Open accessAbstract
Efforts to understand autoimmunity have been pursued relentlessly for several decades. It has become apparent that the immune system evolved multiple mechanisms for controlling self-reactivity, and defects in one or more of these mechanisms can lead to a breakdown of tolerance. Among the multitude of lesions associated with disease, the most common seem to affect peripheral tolerance rather than central tolerance. The initial trigger for both systemic autoimmune disorders and organ-specific autoimmune disorders probably involves the recognition of self or foreign molecules, especially nucleic acids, by innate sensors. Such recognition, in turn, triggers inflammatory responses and the engagement of previously quiescent autoreactive T cells and B cells. Here we summarize the most prominent autoimmune pathways and identify key issues that require resolution for full understanding of pathogenic autoimmunity.
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Autoreactive T cells are detected in both healthy donors and AID patients.
“Autoreactive T cells are detected in both, healthy donors (HDs) and AID patients, 8 but displayed increased proliferation and pro-inflammatory cytokine production in AID. 1,9”
From Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases (2024) · cites this paper as [8]
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- Authors
- Theofilopoulos, A. N., Kono, D. H., & Baccala, R.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Theofilopoulos, Argyrios N
- Venue
- Nature Immunology
- Published
- 2017-06-20
- Volume
- 18
- Issue
- 7
- Pages
- 716-724
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC5791156
- OpenAlex
- W2630573111
- Cited by
- 590
- References
- 150
- Citations by year
- 2026: 43 · 2025: 61 · 2024: 67 · 2023: 81 · 2022: 72 · 2021: 78 · 2020: 78 · 2019: 60 · 2018: 40 · 2017: 9
- FWCI
- 5.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL114408)
- National Institute of Allergy and Infectious Diseases (R21AI117563, R56AI121525)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR068910, R01AR065919)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Keywords
- autoimmunity, immune tolerance, peripheral tolerance, central tolerance, autoreactivity, nucleic acids, autoreactive T cells, autoreactive B cells, systemic autoimmune diseases, inflammation
- MeSH terms
- Animals, Autoimmune Diseases, B-Lymphocytes, Humans, T-Lymphocytes, Autoimmunity, Self Tolerance, Peripheral Tolerance, Central Tolerance
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