ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2015
IL-4/CCL22/CCR4 axis controls regulatory T-cell migration that suppresses inflammatory bone loss in murine experimental periodontitis.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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61 citing papers in PubMed, 106 citations in OpenAlex.
- Review
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- RANKL-convergent osteoimmune network framework in osteoporosis: integrating macrophage activation, T-cell imbalance, and cytokine crosstalk.Frontiers in immunology · 2026Review
- Role of regulatory immune cells in pathogenesis and therapy of periodontitis.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Inflammation-triggered Gli1Cellular & molecular immunology · 2025Article
- Cytokine responses of CD4+ T cells and NKT cells to periodontitis-associated bacteria in individuals with or without periodontitis.Journal of periodontal research · 2025Article
- IRF3 Promotes Production of IL-6 and Nitric Oxide but Represses CCL22 in RAW264.7 Macrophage Cells Exposed to Lipopolysaccharides in Culture.Journal of inflammation research · 2025Article
- M1 and M2 macrophages markers are alternately expressed during periapical lesion development.Journal of applied oral science : revista FOB · 2025Article
- Dynamic changes in macrophage polarization during the resolution phase of periodontal disease.Immunity, inflammation and disease · 2024Article
- Therapeutic delivery of CCL2 modulates immune response and restores host-microbe homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Age-related alveolar bone maladaptation in adult orthodontics: finding new ways out.International journal of oral science · 2024Review
- A Narrative Review of the State of the Art of CCR4-Based Therapies in Cutaneous T-Cell Lymphomas: Focus on Mogamulizumab and Future Treatments.Antibodies (Basel, Switzerland) · 2024Review
- Deficiency of INPP4A promotes M2 macrophage polarization in eosinophilic chronic rhinosinusitis with nasal polyps.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Advances in the research of immunomodulatory mechanism of mesenchymal stromal/stem cells on periodontal tissue regeneration.Frontiers in immunology · 2024Review
- Oral microbiota-host interaction: the chief culprit of alveolar bone resorption.Frontiers in immunology · 2024Review
- The Mechanism of Delayed Ischemic Preconditioning in Alleviating Acute Ischemia/Reperfusion Renal Injury through Treg Mediated by Immature CD11cKidney diseases (Basel, Switzerland) · 2022Article
- Presence of periodontitis may synergistically contribute to cancer progression via Treg and IL-6.Scientific reports · 2022Article
- Immunomodulatory strategies for bone regeneration: A review from the perspective of disease types.Biomaterials · 2022Review
- SNAP25 is a potential prognostic biomarker for prostate cancer.Cancer cell international · 2022Article
1 more citing papers are in PubMed but not listed here.
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11 authors at 4 institutions in 2 countries.
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Abstract
Inflammatory bone resorption is a hallmark of periodontitis, and Tregs and Th2 cells are independently associated with disease progression attenuation. In this study, we employed an infection-triggered inflammatory osteolysis model to investigate the mechanisms underlying Treg and Th2 cell migration and the impact on disease outcome. Aggregatibacter actinomycetemcomitans-infected C57Bl/6 (wild-type [WT]) mice develop an intense inflammatory reaction and alveolar bone resorption, and Treg and Th2 cell migration is temporally associated with disease progression attenuation. Tregs extracted from the lesions preferentially express CCR4 and CCR8, whereas Th2 cells express CCR3, CCR4, and CCR8. The absence of CCR5 and CCR8 did not significantly impact the migration of Tregs and Th2 cells or affect the disease outcome. CCR4KO mice presented a minor reduction in Th2 cells in parallel with major impairment of Treg migration, which was associated with increased inflammatory bone loss and higher proinflammatory and osteoclastogenic cytokine levels. The blockade of the CCR4 ligand CCL22 in WT mice resulted in an increased inflammatory bone loss phenotype similar to that in the CCR4KO strain. Adoptive transfer of CCR4(+) Tregs to the CCR4KO strain revert the increased disease phenotype to WT mice-like levels; also, the in situ production of CCL22 in the lesions is mandatory for Tregs migration and the consequent bone loss arrest. The local release of exogenous CCL22 provided by poly(lactic-co-glycolic acid) (PLGA) microparticles promotes migration of Tregs and disease arrest in the absence of endogenous CCL22 in the IL-4KO strain, characterized by the lack of endogenous CCL22 production, defective migration of Tregs, and exacerbated bone loss. In summary, our results show that the IL-4/CCL22/CCR4 axis is involved in the migration of Tregs to osteolytic lesion sites, and attenuates development of lesions by inhibiting inflammatory migration and the production of proinflammatory and osteoclastogenic mediators.
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