IL-17-producing γδ T cells enhance bone regeneration

Takehito Ono; Kazuo Okamoto; Tomoki Nakashima; Takeshi Nitta; Shohei Hori; Yoichiro Iwakura; Hiroshi Takayanagi

doi:10.1038/ncomms10928

IL-17-producing γδ T cells enhance bone regeneration

Nat Commun. 2016 Mar 11:7:10928. doi: 10.1038/ncomms10928.

Authors

Takehito Ono¹, Kazuo Okamoto^{1

2}, Tomoki Nakashima^{3

4

5}, Takeshi Nitta¹, Shohei Hori⁶, Yoichiro Iwakura⁷, Hiroshi Takayanagi^{1

2}

Affiliations

¹ Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
² Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Program, Takayanagi Osteonetwork Project, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
³ Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549, Japan.
⁴ Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549, Japan.
⁵ Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549, Japan.
⁶ Laboratory for Immune Homeostasis, RIKEN Center for Integrative Medical Science, Suehiro-cho 1-7-22, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
⁷ Research Institute for Biological Sciences, Tokyo University of Science, Yamazaki 2669, Noda, Chiba 278-0022, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Regeneration / immunology*
Cell Differentiation / drug effects
Cell Differentiation / immunology
Femoral Fractures / immunology*
Femur / diagnostic imaging
Femur / immunology*
Femur / injuries
Femur / pathology
Flow Cytometry
Fracture Healing / immunology*
Interleukin-17 / genetics
Interleukin-17 / immunology*
Interleukin-17 / pharmacology
Mice
Mice, Knockout
Osteoblasts / drug effects
Osteogenesis / immunology*
Receptors, Antigen, T-Cell, gamma-delta / genetics
Receptors, Antigen, T-Cell, gamma-delta / immunology
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes / immunology*
X-Ray Microtomography

Substances

Il17a protein, mouse
Interleukin-17
Receptors, Antigen, T-Cell, gamma-delta