2. Academic Validation
  3. Early infiltrating NKT lymphocytes attenuate bone regeneration through secretion of CXCL2

Early infiltrating NKT lymphocytes attenuate bone regeneration through secretion of CXCL2

  • Sci Adv. 2024 May 17;10(20):eadl6343. doi: 10.1126/sciadv.adl6343.
Weimin Lin 1,  Qiwen Li 1,  Linfeng Liu 1,  Qian Wang 1,  Danting Zhang 1,  Feiyu Wang 1,  Ruoshi Xu 1,  Yi Fan 1 2,  Malcolm Xing 3,  Chenchen Zhou 1 4,  Quan Yuan 1 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral Diseases and National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, 610041 Chengdu, Sichuan, China.
  • 2 Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, 610041 Chengdu, Sichuan, China.
  • 3 Department of Mechanical Engineering, University of Manitoba, Winnipeg R3T 2N2, Canada.
  • 4 Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, 610041 Chengdu, Sichuan, China.
  • 5 Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, 610041 Chengdu, Sichuan, China.
PMID: 38758783 DOI: 10.1126/sciadv.adl6343
Abstract

Trauma rapidly mobilizes the immune response of surrounding tissues and activates regeneration program. Manipulating immune response to promote tissue regeneration shows a broad application prospect. However, the understanding of bone healing dynamics at cellular level remains limited. Here, we characterize the landscape of immune cells after alveolar bone injury and reveal a pivotal role of infiltrating natural killer T (NKT) cells. We observe a rapid increase in NKT cells after injury, which inhibit osteogenic differentiation of mesenchymal stem cells (MSCs) and impair alveolar bone healing. Cxcl2 is up-regulated in NKT cells after injury. Systemic administration of CXCL2-neutralizing antibody or genetic deletion of Cxcl2 improves the bone healing process. In addition, we fabricate a gelatin-based porous hydrogel to deliver NK1.1 depletion antibody, which successfully promotes alveolar bone healing. In summary, our study highlights the importance of NKT cells in the early stage of bone healing and provides a potential therapeutic strategy for accelerating bone regeneration.

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