IL-17-producing γδ T cells enhance bone regeneration

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.

Platelet-functionalized three-dimensional poly-ε-caprolactone fibrous scaffold prepared using centrifugal spinning for delivery of growth factors

“…IL-17 was shown to be one of the key regulators in the early phases of bone healing via osteoblast maturation. 21,22 IL-17 was found in high levels in platelets. In addition, IL-1, TNF-α, SDF-1 and GCSF stimulate mesenchymal progenitor cell activation.…”

Local induction of inflammation affects bone formation

“…In mouse models of bone healing, T cells infiltrate the damaged site in a very characteristic pattern. Following an initial peak in the presence of T cells, their numbers drop within a week (Konnecke et al, 2014;Ono et al, 2016). In comparison, a prolonged presence of pro-inflammatory T cells in the fracture hematoma in sheep is associated with delayed bone healing (Schmidt-Bleek et al, 2012).…”

“…Alternatively, their activation could also occur secondarily to the innate immune response (MacLeod et al, 2007;Zanin-Zhorov et al, 2007). The local presence of adaptive immune cells can be both stimulatory (Nam et al, 2012;Ono et al, 2016) or inhibitory (Chatterjea et al, 2014;Liu et al, 2011;Reinke et al, 2013) for bone regeneration, and is likely dependent on the contribution of specific T cell subsets.…”

“…For example, IL-17-producing T cells contribute to bone healing and MSC osteogenesis (Croes et al, 2016;Nam et al, 2012;Ono et al, 2016), while other proinflammatory T cell subsets can also inhibit bone formation (Liu et al, 2011;Reinke et al, 2013). In a follow-up, a functional assay should elucidate whether lymphocytes are actually involved in the bone formation process in this model.…”

“…During this phase, proinflammatory cytokines such as TNF-α, IL-1, IL-6 and IL-17 act together with BMPs and other transforming growth factor family members to induce processes leading to repair and restoration (Cho et al, 2002;Claes et al, 2012;Geusens et al, 2013;Nam et al, 2012;Rundle et al, 2006;Schmidt-Bleek et al, 2015;Yang et al, 2007). Several of these cytokines have stimulatory effects on the osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro Glass et al, 2011;Mountziaris et al, 2011;Ono et al, 2016). A balanced expression of these cytokines seems to…”