ArticleThe Journal of biological chemistry2011
Toll-like receptor 4 (TLR4) is essential for Hsp70-like protein 1 (HSP70L1) to activate dendritic cells and induce Th1 response.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- The association of toll-like receptor 4 gene polymorphisms with primary open angle glaucoma susceptibility: a meta-analysis.Bioscience reports · 2019Pooled it
- Trimetazidine Improves the Outcome of EECP Therapy in Patients with Refractory Angina Pectoris.Medical archives (Sarajevo, Bosnia and Herzegovina) · 2020Trial
- Cardiopulmonary and Immune Effects of Environmental Particulate Exposures.Physiology (Bethesda, Md.) · 2026Review
- MicroRNAs and Alarmins in Cardio-Oncology: Biomarkers and Therapeutic Implications in Skin and Breast Cancer.International journal of molecular sciences · 2026Review
- Acute-on-chronic liver failure and immune dysregulation: Systemic inflammation and immunoparesis paradox.Hepatology communications · 2026Review
- Invasive pulmonary aspergillosis in the ICU: the corticosteroid link.Pneumonia (Nathan Qld.) · 2026Review
- Oxidative stress-driven disease-associated microglia (DAM)-like polarization in human microglia (HMC3) cells exposed to small-size silver nanoparticles in a transwell co-culture system with neurons (cholinergic differentiated SH-SY5Y) cells in vitro.Archives of toxicology · 2026Article
- Taking its TOLL: the role of toll-like receptor 4 in human health and disease, and its potential as a therapeutic target.Frontiers in immunology · 2026Review
- Sp3 ameliorated experimental autoimmune encephalomyelitis by triggering Socs3 in Th17 cells.Journal of advanced research · 2025Article
- Lyn expression in macrophages promotes TLR activation and restricts proliferation in an isoform-independent manner.Journal of leukocyte biology · 2025Article
- Unveiling the Immunostimulatory Potential of the HSPA1A Mini-Chaperones Compared to the HSPA1A and HSP27 Chaperones: In Silico and In Vitro Insights for Vaccine Development.The protein journal · 2025Article
- HSPA2 influences the differentiation and production of immunomodulatory mediators in human immortalized epidermal keratinocyte lines.Cell death & disease · 2025Article
- The Impact of Recreational Diving to a Depth of 40 m on Selected Intracellular DAMPs.International journal of molecular sciences · 2025Article
- Review of BCG immunotherapy for bladder cancer.Clinical microbiology reviews · 2025Review
- The Blood-prostate Barrier: An Obstacle to Drug Delivery into the Prostate.Current drug delivery · 2025Review
- The innate immune response in SARS-CoV2 infection: focus on toll-like receptor 4 in severe disease outcomes.Frontiers in immunology · 2025Review
- Review
- Network Pharmacology Combined With Metabolomics Reveals the Mechanism of Yangxuerongjin Pill Against Type 2 Diabetic Peripheral Neuropathy in Rats.Drug design, development and therapy · 2025Article
- Evaluation of the Choroid Plexus Epithelium Inflammation TLR4/NF-κB/NKCC1 Signal Pathway Activation in the Development of Hydrocephalus.CNS neuroscience & therapeutics · 2024Article
- Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptors (TLRs) play important roles in initiation of innate and adaptive immune responses. Emerging evidence suggests that TLR agonists can serve as potential adjuvant for vaccination. Heat shock proteins (HSPs), functionally serving as TLR4 agonists, have been proposed to act as Th1 adjuvant. We have identified a novel Hsp70 family member, termed Hsp70-like protein 1 (Hsp70L1), shown that Hsp70L1 is a potent T helper cell (Th1) polarizing adjuvant that contributes to antitumor immune responses. However, the underlying mechanism for how Hsp70L1 exerts its Th1 adjuvant activity remains to be elucidated. In this study, we found that Hsp70L1 binds directly to TLR4 on the surface of DCs, activates MAPK and NF-κB pathways, up-regulates I-a(b), CD40, CD80, and CD86 expression and promotes production of TNF-α, IL-1β, and IL-12p70. Hsp70L1 failed to induce such phenotypic maturation and cytokine production in TLR4-deficient DCs, indicating a role for TLR4 in mediating Hsp70L1-induced DC activation. Furthermore, more efficient induction of carcinoembryonic antigen (CEA)-specific Th1 immune response was observed in mice immunized by wild-type DCs pulsed with Hsp70L1-CEA(576-669) fusion protein as compared with TLR4-deficient DCs pulsed with same fusion protein. In addition, TLR4 antagonist impaired induction of CEA-specific human Th1 immune response in a co-culture system of peripheral blood lymphocytes (PBLs) from HLA-A2.1(+) healthy donors and autologous DCs pulsed with Hsp70L1-CEA(576-669) in vitro. Taken together, these results demonstrate that TLR4 is a key receptor mediating the interaction of Hsp70L1 with DCs and subsequently enhancing the induction of Th1 immune response by Hsp70L1/antigen fusion protein.
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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.