Inhibitory receptor agonists: the future of autoimmune disease therapeutics?
Open accessAbstract
Central and peripheral tolerance both contribute to protection against autoimmunity. The pathogenesis of autoimmunity, however, can result from critical deficits or limitations in peripheral and/or central tolerance mechanisms, presenting an opportunity for therapeutic intervention. Recent advances highlight the substantial impact of inhibitory receptors (IRs), which mediate peripheral tolerance, in autoimmunity. Deletion and blockade studies in mice, IR disruption in humans, and correlation with positive disease outcomes all highlight potential clinical benefits of enhancing IR signaling (agonism)-specifically CTLA4, PD1, LAG3, TIM3 and TIGIT-to treat autoimmune disease. Although critical questions remain, IR agonists represent an unappreciated and untapped opportunity for the treatment of autoimmune and inflammatory diseases.
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Exhaustion actively modulates the pathogenic T cell response in patients rather than restricts autoreactivity development in healthy donors.
“further suggesting that exhaustion actively modulates the pathogenic T cell response in patients rather than restricts autoreactivity development in HDs. 61”
From Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases (2024) · cites this paper as [61]
The section on prognosis in human autoimmunity reports that exhaustion-associated signatures predict better flare-free survival and slower type 1 diabetes progression in patients. It also says functional exhaustion in the sampled cells has not been proved. The paper does not establish that exhaustion actively modulates pathogenic T cells rather than restricting the development of autoreactivity in healthy donors. (LLM, conf=0.86)
Experimental — accuracy not yet measuredInhibitory receptor deficiencies or checkpoint therapies can cause or exacerbate AIDs.
“Inhibitory receptor deficiencies or checkpoint therapies can cause or exacerbate AIDs, 37,61”
From Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases (2024) · cites this paper as [61]
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Autoreactive CD8+ T cells are restrained by an exhaustion-like program that is maintained by LAG3
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- Authors
- Grebinoski, S., & Vignali, D. A.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Vignali, Dario AA
- Venue
- Current Opinion in Immunology
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 67
- Pages
- 1-9
- ISSN
- 0952-7915 (ISSN-L)
- PMC
- PMC7744338
- OpenAlex
- W3039660273
- Cited by
- 58
- References
- 75
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 10 · 2023: 11 · 2022: 16 · 2021: 3 · 2020: 2
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- peripheral tolerance, central tolerance, CTLA-4, PD-1, LAG-3, TIM-3, TIGIT, autoimmune disease pathogenesis, inflammatory diseases
- MeSH terms
- Animals, Autoimmune Diseases, Humans, Receptors, Immunologic, Signal Transduction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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