ArticleThe Journal of experimental medicine2023
Construction of a T cell receptor signaling range for spontaneous development of autoimmune disease.
Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 24 citations in OpenAlex.
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- Precision Immunoregulation in transplantation: The rise of engineered Treg therapies.Molecular biology reports · 2026Review
- TCR sequencing in cancer immunology and immunotherapy: what, when, where, why, and how.Journal for immunotherapy of cancer · 2026Review
- Immune-related actinopathies at the cross-road of immunodeficiency, autoimmunity and autoinflammation.Nature reviews. Immunology · 2026Review
- TScience immunology · 2025Article
- Loss of PI3Kδ Activity Drives Autoimmune Colitis by Impairing Extrathymic Treg Differentiation.European journal of immunology · 2025Article
- Interaction between haploinsufficiency of PTPN2 and patient microbiome promotes autoimmune arthritis in mice.Journal of autoimmunity · 2025Article
- The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases.Nature reviews. Immunology · 2024Review
- Targeting tumor-infiltrating tregs for improved antitumor responses.Frontiers in immunology · 2024Review
- Defective LAT signalosome pathology in mice mimics human IgG4-related disease at single-cell level.The Journal of experimental medicine · 2023Article
- High-dimensional analysis of T-cell profiling variations following belimumab treatment in systemic lupus erythematosus.Lupus science & medicine · 2023Article
- Regulatory T cells in autoimmune kidney diseases and transplantation.Nature reviews. Nephrology · 2023Review
- Transcription factor EGR2 controls homing and pathogenicity of TNature immunology · 2023Article
- Treg-based immunotherapy for antigen-specific immune suppression and stable tolerance induction: a perspective.Immunotherapy advances · 2023Review
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21 authors at 6 institutions in 3 countries.
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Abstract
Thymic selection and peripheral activation of conventional T (Tconv) and regulatory T (Treg) cells depend on TCR signaling, whose anomalies are causative of autoimmunity. Here, we expressed in normal mice mutated ZAP-70 molecules with different affinities for the CD3 chains, or wild type ZAP-70 at graded expression levels under tetracycline-inducible control. Both manipulations reduced TCR signaling intensity to various extents and thereby rendered those normally deleted self-reactive thymocytes to become positively selected and form a highly autoimmune TCR repertoire. The signal reduction more profoundly affected Treg development and function because their TCR signaling was further attenuated by Foxp3 that physiologically repressed the expression of TCR-proximal signaling molecules, including ZAP-70, upon TCR stimulation. Consequently, the TCR signaling intensity reduced to a critical range generated pathogenic autoimmune Tconv cells and concurrently impaired Treg development/function, leading to spontaneous occurrence of autoimmune/inflammatory diseases, such as autoimmune arthritis and inflammatory bowel disease. These results provide a general model of how altered TCR signaling evokes autoimmune disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.