T cell related osteoimmunology in fracture healing: Potential targets for augmenting bone regeneration
Haixing Wang, Yi-Long Li, Haoxin Li, Yan Xu, Zhaowei Jiang, Feng Lu, Wenhui Hu, Yinuo Fan, Sien Lin, Gang Li
Abstract
Last decade has witnessed increasing evidence which highlights the roles of immune cells in bone regeneration. Numerous immune cell types, including macrophages, T cells, and neutrophils are involved in fracture healing by orchestrating a series of events that modulate bone formation and remodeling. In this review, the role of T cell immunity in fracture healing has been summarized, and the modulatory effects of T cell immunity in inflammation, bone formation and remodeling have been highlighted. The review also summarizes the specific roles of different T cell subsets, including CD4 + T cells, CD8 + T cells, regulatory T cells, T helper 17 cells, and γδ T cells in modulating fracture healing. The current therapeutics targeting T cell immunity to enhance fracture healing have also been reviewed, aiming to provide insights from a translational standpoint. Overall, this work discusses recent advances and challenges in the interdisciplinary research field of T cell related osteoimmunology and its implications in fracture healing. Delayed unions or non-unions of bone fractures remain a challenge in clinical practice. Developing a deep understanding of the roles of immune cells, including T cells, in fracture healing will facilitate the advancement of novel therapeutics of fracture nonunion. This review summarizes the current understanding of different T cell subsets involved in various phases of fracture healing, providing insights for targeting T cells as an alternative strategy to enhance bone regeneration.