IL-17-producing γδ T cells enhance bone regeneration

Immune responses are crucial not only for host defence against pathogens but also for tissue maintenance and repair after injury. Lymphocytes are involved in the healing process after tissue injury, including bone fracture and muscle damage. However, the specific immune cell subsets and mediators of healing are not entirely clear. Here we show that γδ T cells produce IL-17A, which promotes bone formation and facilitates bone fracture healing. Repair is impaired in IL-17A-deficient mice due to a defect in osteoblastic bone formation. IL-17A accelerates bone formation by stimulating the proliferation and osteoblastic differentiation of mesenchymal progenitor cells. This study identifies a novel role for IL-17-producing γδ T cells in skeletal tissue regeneration. γδ T cells are innate-like lymphocytes that regulate immune responses by producing IL-17A or IFN-γ, but have no known role in bone healing. Here the authors show a nonimmune bone-regenerative function of IL-17A produced by the Vγ6+ subset in mice.

• Publication year

  2016

• Venue

  Nature Communications

• Publication date

  2016-03-11

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/ncomms10928PMID 26965320PMCID 4792964
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• A novel IL-17 signaling pathway controlling keratinocyte proliferation and tumorigenesis via the TRAF4–ERK5 axis

  2015cited by this paper
• Fracture healing: mechanisms and interventions

  2015cited by this paper
• Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial.

  2015cited by this paper
• The IL-23–IL-17 immune axis: from mechanisms to therapeutic testing

  2014cited by this paper
• IL-17 inhibits osteoblast differentiation and bone regeneration in rat.

  2014cited by this paper
• Role of Fas and Treg Cells in Fracture Healing as Characterized in the Fas-Deficient (lpr) Mouse Model of Lupus†

  2014cited by this paper
• Six-of-the-best: unique contributions of γδ T cells to immunology

  2013cited by this paper
• Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial.

  2013cited by this paper
• A special population of regulatory T cells potentiates muscle repair.

  2013cited by this paper
• Terminally Differentiated CD8+ T Cells Negatively Affect Bone Regeneration in Humans

  2013cited by this paper
• Fgf9 from dermal γδ T cells induces hair follicle neogenesis after wounding

  2013cited by this paper
• Interleukin 17 inhibits myogenic and promotes osteogenic differentiation of C2C12 myoblasts by activating ERK1,2.

  2012cited by this paper
• Plasticity of Foxp3(+) T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells.

  2012cited by this paper
• The CD100 receptor interacts with its plexin B2 ligand to regulate epidermal γδ T cell function.

  2012cited by this paper
• T-Lymphocytes Enable Osteoblast Maturation via IL-17F during the Early Phase of Fracture Repair

  2012cited by this paper
• IL-23 induces spondyloarthropathy by acting on ROR-γt+ CD3+CD4−CD8− entheseal resident T cells

  2012cited by this paper
• Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration.

  2012cited by this paper
• Osteoprotection by semaphorin 3A

  2012cited by this paper
• Suppression of bone formation by osteoclastic expression of semaphorin 4D

  2011cited by this paper
• Fracture healing is accelerated in the absence of the adaptive immune system

  2010cited by this paper
• γδ T cell effector functions: a blend of innate programming and acquired plasticity

  2010cited by this paper
• Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow

  2009cited by this paper
• IL-17 stimulates the proliferation and differentiation of human mesenchymal stem cells: implications for bone remodeling

  2009cited by this paper
• Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals.

  2009cited by this paper
• Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses.

  2009cited by this paper
• Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity.

  2009cited by this paper
• The roles of IL‐17A in inflammatory immune responses and host defense against pathogens

  2008cited by this paper
• Hematopoietic stem-cell contribution to ectopic skeletogenesis.

  2007cited by this paper
• Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction

  2006cited by this paper
• Bisphosphonate (YM529) delays the repair of cortical bone defect after drill-hole injury by reducing terminal differentiation of osteoblasts in the mouse femur.

  2005cited by this paper
• Subset-specific, uniform activation among V gamma 6/V delta 1+ gamma delta T cells elicited by inflammation.

  2004cited by this paper
• Subset‐specific, uniform activation among Vγ6/Vδ1+ γδ T cells elicited by inflammation

  2004cited by this paper
• Use of a new adhesive film for the preparation of multi-purpose fresh-frozen sections from hard tissues, whole-animals, insects and plants.

  2003cited by this paper
• IL-17 production from activated T cells is required for the spontaneous development of destructive arthritis in mice deficient in IL-1 receptor antagonist

  2003cited by this paper
• Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses.

  2002cited by this paper
• IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis.

  1999cited by this paper
• Diversity of murine gamma genes and expression in fetal and adult T lymphocytes

  1986cited by this paper
• randomised double blind placebo controlled trial

  year unknowncited by this paper
• Mini Review Article Molecular Mechanisms of Differentiation of Murine Pro-inflammatory Γδ T Cell Subsets Roles of Ifn-γ and Il-17-producing Γδ T Cells in Immune Responses

  year unknowncited by this paper
• Interleukin-17-Producing gd T Cells Selectively Expand in Response to Pathogen Products and Environmental Signals

  year unknowncited by this paper

• Biological Principles for Success in Alveolar Bone, Soft Tissue, and Periodontal Regeneration.

  2026cites this paper
• Interleukin‐17A‐Producing Gamma Delta T Cells Accelerate Mineralization in Human Dental Pulp Stem Cells

  2026influential citation
• Immune Involvement in the Development and Maintenance of Oral and Craniofacial Bones.

  2026cites this paper
• Immunomodulation Strategies to Enhance Oral Bone Regeneration.

  2026cites this paper
• Osteoimmune Regulation in Dental Implant Osseointegration: From Foreign Body Response to Therapeutic Immunomodulation—A Narrative Review

  2026cites this paper
• Biomaterial-assisted gene therapy for bone repair.

  2026cites this paper
• Musculoskeletal Diseases: Mechanisms and Therapeutic Advances

  2025cites this paper
• Identification of aging-related biomarkers for intervertebral disc degeneration in whole blood samples based on bioinformatics and machine learning

  2025cites this paper
• Local Delivery of Lipid-based Nanoparticles Containing Microbial Nucleic Acid for Osteoimmunomodulation.

  2025cites this paper
• Fine Line Between Repair & Ruin: How Inflammation Shapes Bone Remodelling?

  2025cites this paper
• Bioaugmented osteosynthesis: precise monitoring and intervention of the bone healing microenvironment

  2025cites this paper
• Osteoimmunomodulation by bone implant materials: harnessing physicochemical properties and chemical composition.

  2025cites this paper
• Advances in hydrogel systems for bone regeneration: trends, innovations, and prospects.

  2025cites this paper
• γδ T cells in Escherichia coli infection.

  2025cites this paper
• Beyond natural silk: Bioengineered silk fibroin for bone regeneration

  2025cites this paper
• Tap1 knockdown promotes osteogenic differentiation via Wnt/β-catenin and ERK1/2 MAPK axes

  2025cites this paper
• Anatomical reassessment of the rat cortical drill-hole injury model

  2025cites this paper
• Immune cell profiles and predictive modeling in osteoporotic vertebral fractures using XGBoost machine learning algorithms

  2025cites this paper
• Intraepithelial lymphocytes in human oral diseases

  2025cites this paper
• The interrelationship between interleukin-17 A and the immunomodulation of mesenchymal stromal cells

  2025cites this paper
• Non-contact electrical stimulation via a Vector-potential transformer promotes bone healing in drill-hole injury model

  2025cites this paper
• Mechanisms of ossification of the entheses in spondyloarthritis physiopathogenic aspects and possible therapeutic implication.

  2025cites this paper
• What can Animal Models tell us About T Cells in Spondyloarthritis Pathogenesis?

  2025cites this paper
• The dual role of IL-17 in periodontitis regulating immunity and bone homeostasis

  2025cites this paper
• A bad break: mechanisms and assessment of acute and chronic pain after bone fracture

  2025cites this paper
• Beyond inflammation: the molecular basis of bone remodeling in axial spondyloarthritis and psoriatic arthritis

  2025cites this paper
• Linker minimization and characterization of fc-fused interleukin-17A for increased in vivo half-life.

  2025cites this paper
• γδ17 T cell-stromal networks modulate matrix composition and vascularity in foreign body response

  2025cites this paper
• Recent progress in immunomodulation-based strategies for bone repair

  2025cites this paper
• Potential of organ-on-a-chip in advancing synthetic extracellular matrix technology for bone tissue engineering in dentistry (Review)

  2025cites this paper
• TSG-6 promotes healing of critical-sized bone defects in mice

  2025cites this paper
• Human spinal enthesis comparative biology of IL-17F and IL-17A reveals greater T-cell IL-17F induction and IL-23 regulation

  2025cites this paper
• γδ17T Cells Hinder Mandibular Bone Defect Healing.

  2025cites this paper
• T cell related osteoimmunology in fracture healing: Potential targets for augmenting bone regeneration

  2025influential citation
• The recent progress of γδ T cells and its targeted therapies in rheumatoid arthritis

  2024cites this paper
• Crosstalk between bone and the immune system

  2024cites this paper
• The immunologic role of IL-23 in psoriatic arthritis: a potential therapeutic target

  2024cites this paper
• T细胞免疫在骨重建和骨再生中的研究进展

  2024cites this paper
• The Microbial Revolution in the World of Joint Replacement Surgery

  2024cites this paper
• Construction Form and Application of Three-Dimensional Bioprinting Ink Containing Hydroxyapatite

  2024cites this paper
• Innate immune response to bone fracture healing.

  2024cites this paper
• IL-17RA Signaling in Prx1+ Mesenchymal Cells Influences Fracture Healing in Mice

  2024influential citation
• Emilin2 marks the target region for mesenchymal cell accumulation in bone regeneration

  2024cites this paper
• γδ T cells in oral diseases

  2024cites this paper
• A RORE-dependent Intronic Enhancer in the IL-7 Receptor-α Locus Controls Glucose Metabolism via Vγ4+ γδT17 Cells.

  2024cites this paper
• Osteoimmunology: The Crosstalk between T Cells, B Cells, and Osteoclasts in Rheumatoid Arthritis

  2024cites this paper
• The impact of arthritogenic viruses in oral tissues.

  2024cites this paper
• Immunoengineering Biomaterials for Musculoskeletal Tissue Repair across Lifespan

  2024cites this paper
• CD4+ and CD8+ T Cells Reduce Inflammation and Promote Bone Healing in Response to Titanium Implants.

  2024cites this paper
• Modulation of fracture healing by senescence-associated secretory phenotype (SASP): a narrative review of the current literature

  2024cites this paper
• Interaction between immuno-stem dual lineages in jaw bone formation and injury repair

  2024cites this paper
• Advanced Immunomodulatory Biomaterials for Therapeutic Applications

  2024cites this paper
• Tacrolimus, FK506, promotes bone formation in bone defect mouse model.

  2024cites this paper
• Osteoimmunology of Fracture Healing

  2024cites this paper
• Analysis of Infiltrating Immune Cells Following Intervertebral Disc Injury Reveals Recruitment of Gamma-Delta (γδ) T cells in Female Mice

  2024cites this paper
• Cellular and molecular mechanisms underlying obesity in degenerative spine and joint diseases

  2024cites this paper
• Network Pharmacology Approach to Acalypha indica L. and Plumbago zeylanica L. As Anti-Rheumatoid Arthritis Candidates

  2024cites this paper
• Advances in the application and research of biomaterials in promoting bone repair and regeneration through immune modulation

  2024cites this paper
• Sex-specific divergences in the types and timing of infiltrating immune cells during the intervertebral disc acute injury response and their associations with degeneration

  2024cites this paper
• Inflammation and mechanical force-induced bone remodeling.

  2024cites this paper
• The role of ixekizumab in the treatment of nonradiographic axial spondyloarthritis.

  2024cites this paper
• IL-17A Levels and Progression of Kidney Disease Following Hospitalization with and without Acute Kidney Injury

  2024cites this paper
• The balance between helper T 17 and regulatory T cells in osteoimmunology and relevant research progress on bone tissue engineering

  2024cites this paper
• Trained innate immunity modulates osteoblast and osteoclast differentiation

  2024cites this paper
• IL-17 inhibitors in axial spondyloarthritis. An overview

  2024cites this paper
• Imaging in psoriatic arthritis: established methods and emerging techniques

  2024cites this paper
• Four-Dimensional Perspective on Biomimetic Design and Fabrication of Bone Scaffolds for Comprehensive Bone Regeneration

  2024cites this paper
• Bone formation ability of Gli1+ cells in the periodontal ligament after tooth extraction.

  2023cites this paper
• Delayed cortical bone healing due to impaired nuclear Nrf2 translocation in COPD mice.

  2023cites this paper
• Direct Knockdown of PDZ and LIM Domain 1 Using an Adenoviral Delivery System Accelerates Osteogenesis and Fracture Healing in Mice

  2023cites this paper
• MicroRNA in medication related osteonecrosis of the jaw: a review

  2023cites this paper
• Bone regeneration in inflammation with aging and cell-based immunomodulatory therapy

  2023cites this paper
• Immune Dysfunction in Medication-Related Osteonecrosis of the Jaw

  2023cites this paper
• T cells heal bone fractures with help from the gut microbiome.

  2023cites this paper
• The Role of T Lymphocytes in Bone Remodeling

  2023cites this paper
• Potential therapeutic targets beyond cytokines and Janus kinases for autoimmune arthritis.

  2023cites this paper
• The role of γδ T cells in the immunopathogenesis of inflammatory diseases: From basic biology to therapeutic targeting.

  2023cites this paper
• Segmental defect healing in the presence or absence of recombinant human BMP2: Novel insights from a rat model

  2023cites this paper
• Distinctive role of inflammation in tissue repair and regeneration

  2023cites this paper
• Callus γδ T cells and microbe-induced intestinal Th17 cells improve fracture healing in mice

  2023cites this paper
• γδT cells in oral tissue immune surveillance and pathology

  2023cites this paper
• The decisive early phase of bone regeneration

  2023cites this paper
• New Insights into the Role of Synovial Fibroblasts Leading to Joint Destruction in Rheumatoid Arthritis

  2023cites this paper
• Results of flow cytometric detection of gamma-deltaT cells in peripheral blood of patients with ankylosing spondylitis: a pilot study.

  2023cites this paper
• The dichotomic role of single cytokines: Fine-tuning immune responses.

  2023cites this paper
• Structural disease modification in axial spondyloarthritis.

  2023cites this paper
• The IL-17-IL-17RA axis is required to promote osteosarcoma progression in mice

  2023cites this paper
• Effect of T cells on bone.

  2023cites this paper
• The role of toll-like receptors in orchestrating osteogenic differentiation of mesenchymal stromal cells and osteoimmunology

  2023cites this paper
• Results of flow cytometric detection of γδT cells in peripheral blood of patients with ankylosing spondylitis: a pilot study

  2023cites this paper
• Cellular plasticity of the bone marrow niche promotes hematopoietic stem cell regeneration

  2023cites this paper
• The function of immunomodulation and biomaterials for scaffold in the process of bone defect repair: A review

  2023cites this paper
• Medication-related osteonecrosis of the jaw (MRONJ): a review of pathogenesis hypothesis and therapy strategies

  2023cites this paper
• Oral Biosciences: The annual review 2022.

  2023cites this paper
• The IL-17 family in diseases: from bench to bedside

  2023cites this paper
• Systemic inflammatory and gut microbiota responses to fracture in young and middle-aged mice

  2023cites this paper
• Association of Immune Cell Subsets with Incident Hip Fracture: The Cardiovascular Health Study

  2023cites this paper
• Subcutaneously Transplanted Fresh Cartilage in Allogeneic and Xenogeneic Immunocompetent Mouse

  2023cites this paper
• Correlations between Immune Response and Etiopathogenic Factors of Medication-Related Osteonecrosis of the Jaw in Cancer Patients Treated with Zoledronic Acid

  2023cites this paper
• Bone Involvement in Rheumatoid Arthritis and Spondyloartritis: An Updated Review

  2023cites this paper