ArticleProceedings of the National Academy of Sciences of the United States of America2013
Excessive Th1 responses due to the absence of TGF-β signaling cause autoimmune diabetes and dysregulated Treg cell homeostasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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60 citing papers in PubMed, 82 citations in OpenAlex.
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- TIF1γ regulates stability of regulatory T cells during inflammation.Nature immunology · 2026Article
- Gene regulatory network determinants of rapid recall in human memory CD4Cell reports · 2026Article
- Synthetic Immunological Niche Reveals Early Immune Dysregulation and Stratifies Therapeutic Response in Type 1 Diabetes.bioRxiv : the preprint server for biology · 2026Article
- TGFβ limits proximal CD8+ TCR signaling via PTPN22 following strong and moderate agonism.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Preclinical Diagnosis of Type 1 Diabetes: Reality or Utopia.Biomedicines · 2025Review
- CD2 targeted nanoparticles containing IL-2 mimic fetal-maternal tolerance of pregnancy by inducing synergistic TGF-β-producing NK cells and Tregs.Frontiers in immunology · 2025Article
- Immunomodulatory mechanisms of the gut microbiota and metabolites on regulatory T cells in rheumatoid arthritis.Frontiers in immunology · 2025Review
- CD2-targeted nanoparticles encapsulating IL-2 induce tolerogenic Tregs and TGF-β-producing NK cells that stabilize Tregs for long-term therapeutic efficacy in immune-mediated disorders.Frontiers in immunology · 2025Article
- Gaps in maternal-fetal interface rejection response: chronic histiocytic intervillositis.Frontiers in immunology · 2025Review
- Dairy: Friend or Foe? Bovine Milk-Derived Extracellular Vesicles and Autoimmune Diseases.International journal of molecular sciences · 2024Review
- IFNγ at the early stage induced after cryo-thermal therapy maintains CD4Frontiers in immunology · 2024Article
- Crosstalk between efferocytic myeloid cells and T-cells and its relevance to atherosclerosis.Frontiers in immunology · 2024Review
- Intricacies of TGF-β signaling in Treg and Th17 cell biology.Cellular & molecular immunology · 2023Review
- Inhibition of DYRK1B suppresses inflammation in allergic contact dermatitis model and Th1/Th17 immune response.Scientific reports · 2023Article
- Inhibition of NLRP3 inflammasome activity by MCC950 leads to exacerbation of Sjӧgren's syndrome pathologies in non-obese diabetic mice.Immunology · 2023Article
- 4-Hexylresorcinol: pharmacologic chaperone and its application for wound healing.Maxillofacial plastic and reconstructive surgery · 2022Review
- Regulatory T Cells in Autoimmune Vasculitis.Frontiers in immunology · 2022Review
- Updates on immunological mechanistic insights and targeting of the oral lichen planus microenvironment.Frontiers in immunology · 2022Review
- TGFβ: Signaling Blockade for Cancer Immunotherapy.Annual review of cancer biology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
TGF-β signaling in T cells is critical for peripheral T-cell tolerance by regulating effector CD4(+) T helper (Th) cell differentiation. However, it is still controversial to what extent TGF-β signaling in Foxp3(+) regulatory T (Treg) cells contributes to immune homeostasis. Here we showed that abrogation of TGF-β signaling in thymic T cells led to rapid type 1 diabetes (T1D) development in NOD mice transgenic for the BDC2.5 T-cell receptor. Disease development in these mice was associated with increased peripheral Th1 cells, whereas Th17 cells and Foxp3(+) Treg cells were reduced. Blocking of IFN-γ signaling alone completely suppressed diabetes development in these mice, indicating a critical role of Th1 cells in this model. Furthermore, deletion of TGF-β signaling in peripheral effector CD4(+) T cells, but not Treg cells, also resulted in rapid T1D development, suggesting that conventional CD4(+) T cells are the main targets of TGF-β to suppress T1D. TGF-β signaling was dispensable for Treg cell function, development, and maintenance, but excessive IFN-γ production due to the absence of TGF-β signaling in naive CD4(+) T cells indirectly caused dysregulated Treg cell homeostasis. We further showed that T cell-derived TGF-β1 was critical for suppression of Th1 cell differentiation and T1D development. These results indicate that autocrine/paracrine TGF-β signaling in diabetogenic CD4(+) T cells, but not Treg cells, is essential for controlling T1D development.
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