IL-17-producing γδ T cells enhance bone regeneration
Takehito Ono,Kazuo Okamoto,Tomoki Nakashima,Takeshi Nitta,Shohei Hori,Yoichiro Iwakura,Hiroshi Takayanagi +6 more
TLDR
A novel role is identified for IL-17-producing γδ T cells in skeletal tissue regeneration by stimulating the proliferation and osteoblastic differentiation of mesenchymal progenitor cells and promoting bone formation and bone fracture healing.Abstract:
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.read more
Citations
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Promoting tissue regeneration by modulating the immune system.
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Biomaterials: Foreign Bodies or Tuners for the Immune Response?
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Osteoimmunology: evolving concepts in bone–immune interactions in health and disease
TL;DR: It is well known that immune cells can have profound effects on bone cells, but this interaction is not unidirectional, so Tsukasaki and Takayanagi explore the reciprocal dialogue between bone cells and immune cells during health and disease.
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Osteoimmunology: The Conceptual Framework Unifying the Immune and Skeletal Systems
Kazuo Okamoto,Tomoki Nakashima,Masahiro Shinohara,Takako Negishi-Koga,Noriko Komatsu,Asuka Terashima,Shinichiro Sawa,Takeshi Nitta,Hiroshi Takayanagi +8 more
TL;DR: The function, gene regulation, and signal transduction of osteoimmune molecules, including RANKL, in the context of osteoclastogenesis as well as multiple other regulatory functions are reviewed.
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Mechanisms of bone development and repair
TL;DR: The isolation of a single skeletal stem cell population through cell surface markers and the development of single-cell technologies are enabling precise elucidation of cellular activity and fate during bone repair by providing key insights into the mechanisms that maintain and regenerate bone during homeostasis and repair.
References
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IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis
Shigeru Kotake,Nobuyuki Udagawa,Naoyuki Takahashi,Kenichiro Matsuzaki,Kanami Itoh,Shigeru Ishiyama,Seiji Saito,Kazuhiko Inoue,Naoyuki Kamatani,Matthew T. Gillespie,T. John Martin,Tatsuo Suda +11 more
TL;DR: It is suggested that IL-17 first acts on osteoblasts, which stimulates both COX-2-dependent PGE2 synthesis and ODF gene expression, which in turn induce differentiation of osteoclast progenitors into mature osteoclasts, and that IL -17 is a crucial cytokine for osteoclastic bone resorption in RA patients.
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Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity.
Caroline E. Sutton,Stephen J. Lalor,Cheryl M. Sweeney,Corinna F. Brereton,Ed C. Lavelle,Kingston H. G. Mills +5 more
TL;DR: It is shown that gammadelta T cells express IL-23R and the transcription factor RORgammat and produce IL-17, IL-21, and IL-22 in response to IL-1beta andIL-23, without T cell receptor engagement.
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Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction
Kojiro Sato,Ayako Suematsu,Kazuo Okamoto,Akira Yamaguchi,Yasuyuki Morishita,Yuho Kadono,Sakae Tanaka,Tatsuhiko Kodama,Shizuo Akira,Yoichiro Iwakura,Daniel J. Cua,Hiroshi Takayanagi +11 more
TL;DR: Th17 is a powerful therapeutic target for the bone destruction associated with T cell activation and the interleukin (IL)-23–IL-17 axis, rather than the IL-12–IFN-γ axis, is critical for the onset phase of autoimmune arthritis.
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The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing
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Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses
Susumu Nakae,Yutaka Komiyama,Aya Nambu,Katsuko Sudo,Michiko Iwase,Ikuo Homma,Kenji Sekikawa,Masahide Asano,Masahide Asano,Yoichiro Iwakura +9 more
TL;DR: It is found that contact, delayed-type, and airway hypersensitivity responses, as well as T-dependent antibody production, were significantly reduced in the mutant mice, while IL-17 deficiency of donor T cells did not affect acute graft-versus-host reaction.