ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Osteoclast-Primed Foxp3+ CD8 T Cells Induce T-bet, Eomesodermin, and IFN-γ To Regulate Bone Resorption.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- The role of CD8Frontiers in immunology · 2026Pooled it
- Targeting the gut-bone axis in osteoporosis: probiotic interventions and other microbiota-based therapeutic strategies.Gut microbes · 2026Review
- Opposing Dynamics of CD4 + Regulatory and CD8 + Foxp3+ T Cells Characterize Immune Imbalance in Rheumatoid Arthritis.Inflammation · 2026Article
- Targeting Periodontitis with Treg-Derived Extracellular Vesicles: Modulation of Macrophages and CD8International journal of molecular sciences · 2026Article
- Osteoimmunology: interactions of the bone and immune system.Frontiers in immunology · 2026Review
- The hidden driver of osteoporosis: mitochondria-dominated inflammation.Cell communication and signaling : CCS · 2025Review
- Smoking and osteoimmunology: Understanding the interplay between bone metabolism and immune homeostasis.Journal of orthopaedic translation · 2024Review
- Disulfidptosis-related Protein RPN1 may be a Novel Anti-osteoporosis Target of Kaempferol.Combinatorial chemistry & high throughput screening · 2024Article
- Osteoporosis: interferon-gamma-mediated bone remodeling in osteoimmunology.Frontiers in immunology · 2024Review
- Remodeling of the osteoimmune microenvironment after biomaterials implantation in murine tibia: Single-cell transcriptome analysis.Bioactive materials · 2023Article
- The effect ofFrontiers in immunology · 2023Review
- Mechanisms by which kidney-tonifying Chinese herbs inhibit osteoclastogenesis: Emphasis on immune cells.Frontiers in pharmacology · 2023Review
- Identification of key immune genes of osteoporosis based on bioinformatics and machine learning.Frontiers in endocrinology · 2023Article
- The Multiple Biological Functions of Dipeptidyl Peptidase-4 in Bone Metabolism.Frontiers in endocrinology · 2022Review
- Multinucleated Giant Cells: Current Insights in Phenotype, Biological Activities, and Mechanism of Formation.Frontiers in cell and developmental biology · 2022Review
- Small Molecule Inhibitors Targeting Nuclear Factor κB Activation Markedly Reduce Expression of Interleukin-2, but Not Interferon-γ, Induced by Phorbol Esters and Calcium Ionophores.International journal of molecular sciences · 2021Article
- Innate and adaptive immunity: the understudied driving force of heart valve disease.Cardiovascular research · 2021Review
- Single-cell RNA sequencing of human femoral headAging · 2021Article
- The tethering function of mitofusin2 controls osteoclast differentiation by modulating the CaThe Journal of biological chemistry · 2020Article
- The correlation between the Th17/Treg cell balance and bone health.Immunity & ageing : I & A · 2020Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Osteoimmunology arose from the recognition that cytokines produced by lymphocytes can affect bone homeostasis. We have previously shown that osteoclasts, cells that resorb bone, act as APCs. Cross-presentation of Ags by osteoclasts leads to expression of CD25 and Foxp3, markers of regulatory T cells in the CD8 T cells. Octeoclast-induced Foxp3(+) CD25(+) regulatory CD8 T cells (OC-iTcREG) suppress priming of CD4 and CD8 T cells by dendritic cells. OC-iTcREG also limit bone resorption by osteoclasts, forming a negative feedback loop. In this study, we show that OC-iTcREG express concurrently T-bet and Eomesodermin (Eomes) and IFN-γ. Pharmacological inhibition of IκK blocked IFN-γ, T-bet, and Eomes production by TcREG Furthermore, we show, using chromatin immunoprecipitation, NF-κB enrichment in the T-bet and Eomes promoters. We demonstrate that IFN-γ produced by TcREG is required for suppression of osteoclastogenesis and for degradation of TNFR-associated factor 6 in osteoclast precursors. The latter prevents signaling by receptor activator of NF-κB ligand needed for osteoclastogenesis. Knockout of IFN-γ rendered TcREG inefficient in preventing actin ring formation in osteoclasts, a process required for bone resorption. TcREG generated in vivo using IFN-γ(-/-) T cells had impaired ability to protect mice from bone resorption and bone loss in response to high-dose receptor activator of NF-κB ligand. The results of this study demonstrate a novel link between NF-κB signaling and induction of IFN-γ in TcREG and establish an important role for IFN-γ in TcREG-mediated protection from bone loss.
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