ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Tim-3 pathway controls regulatory and effector T cell balance during hepatitis C virus infection.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 101 citations in OpenAlex.
- Longitudinal assessment of T cell inhibitory receptors in liver transplant recipients and their association with posttransplant infections.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2018Trial
- MicroRNA-155 regulates interferon-γ production in natural killer cells via Tim-3 signalling in chronic hepatitis C virus infection.Immunology · 2015Trial
- Enhanced suppressor function of TIM-3+ FoxP3+ regulatory T cells.European journal of immunology · 2014Trial
- Unveiling the nexus between direct-acting antivirals in hepatitis C virus elimination and immune response.Clinical and experimental medicine · 2025Review
- The homeostasis and heterogeneity of regulatory T cells in sepsis.Burns & trauma · 2025Article
- Revealing the mechanisms and therapeutic potential of immune checkpoint proteins across diverse protein families.Frontiers in immunology · 2025Review
- TIM-3 signaling contributes to the suppressive capacity of Tregs from people with HIV on antiretroviral therapy.Journal of leukocyte biology · 2023Article
- Increase in Serum Soluble Tim-3 Level Is Related to the Progression of Diseases After Hepatitis Virus Infection.Frontiers in medicine · 2022Article
- TIM-3 as a potential exhaustion marker in CD4Immunity, inflammation and disease · 2021Article
- Immune Activation Induces Telomeric DNA Damage and Promotes Short-Lived Effector T Cell Differentiation in Chronic HCV Infection.Hepatology (Baltimore, Md.) · 2021Article
- The TIM3/Gal9 signaling pathway: An emerging target for cancer immunotherapy.Cancer letters · 2021Article
- Tim-3 is dispensable for allergic inflammation and respiratory tolerance in experimental asthma.PloS one · 2021Article
- Immune Checkpoint Inhibitors as Monotherapy or Within a Combinatorial Strategy in Advanced Hepatocellular Carcinoma.International journal of molecular sciences · 2020Review
- Direct-acting antiviral treatment downregulates immune checkpoint inhibitor expression in patients with chronic hepatitis C.Clinical and experimental medicine · 2020Article
- Visualizing Dynamic Changes at the Maternal-Fetal Interface Throughout Human Pregnancy by Mass Cytometry.Frontiers in immunology · 2020Article
- 1,25‑Dihydroxy‑Vitamin D3 induces macrophage polarization to M2 by upregulating T‑cell Ig‑mucin‑3 expression.Molecular medicine reports · 2019Article
- Diagnostic and therapeutic potential of the gut microbiota in patients with early hepatocellular carcinoma.Therapeutic advances in medical oncology · 2019Review
- Hyperprogressive disease: recognizing a novel pattern to improve patient management.Nature reviews. Clinical oncology · 2018Review
- Hyperprogressive Disease in Patients With Advanced Non-Small Cell Lung Cancer Treated With PD-1/PD-L1 Inhibitors or With Single-Agent Chemotherapy.JAMA oncology · 2018Article
- Insufficiency of DNA repair enzyme ATM promotes naive CD4 T-cell loss in chronic hepatitis C virus infection.Cell discovery · 2018Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Hepatitis C virus (HCV) is remarkable at disrupting human immunity to establish chronic infection. Upregulation of inhibitory signaling pathways (such as T cell Ig and mucin domain protein-3 [Tim-3]) and accumulation of regulatory T cells (Tregs) play pivotal roles in suppressing antiviral effector T cell (Teff) responses that are essential for viral clearance. Although the Tim-3 pathway has been shown to negatively regulate Teffs, its role in regulating Foxp3(+) Tregs is poorly explored. In this study, we investigated whether and how the Tim-3 pathway alters Foxp3(+) Treg development and function in patients with chronic HCV infection. We found that Tim-3 was upregulated, not only on IL-2-producing CD4(+)CD25(+)Foxp3(-) Teffs, but also on CD4(+)CD25(+)Foxp3(+) Tregs, which accumulate in the peripheral blood of chronically HCV-infected individuals when compared with healthy subjects. Tim-3 expression on Foxp3(+) Tregs positively correlated with expression of the proliferation marker Ki67 on Tregs, but it was inversely associated with proliferation of IL-2-producing Teffs. Moreover, Foxp3(+) Tregs were found to be more resistant to, and Foxp3(-) Teffs more sensitive to, TCR activation-induced cell apoptosis, which was reversible by blocking Tim-3 signaling. Consistent with its role in T cell proliferation and apoptosis, blockade of Tim-3 on CD4(+)CD25(+) T cells promoted expansion of Teffs more substantially than Tregs through improving STAT-5 signaling, thus correcting the imbalance of Foxp3(+) Tregs/Foxp3(-) Teffs that was induced by HCV infection. Taken together, the Tim-3 pathway appears to control Treg and Teff balance through altering cell proliferation and apoptosis during HCV infection.
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Registered trials
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.