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Article

The Mandible Ameliorates Facial Allograft Rejection and Is Associated with the Development of Regulatory T Cells and Mixed Chimerism

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Department of Plastic Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
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Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
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Department of Head and Neck Surgery, National Police Hospital, Lima 15072, Peru
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Department of Plastic Surgery, Clínica IPS Universitaria León XIII, University of Antioquia, Medellín 050010, Colombia
5
College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Loredana Frasca
Int. J. Mol. Sci. 2021, 22(20), 11104; https://doi.org/10.3390/ijms222011104
Received: 10 September 2021 / Revised: 7 October 2021 / Accepted: 11 October 2021 / Published: 14 October 2021
(This article belongs to the Special Issue T-Regulatory Cells in Autoimmunity and Transplantation)
Vascularized composite allografts contain various tissue components and possess relative antigenicity, eliciting different degrees of alloimmune responses. To investigate the strategies for achieving facial allograft tolerance, we established a mouse hemiface transplant model, including the skin, muscle, mandible, mucosa, and vessels. However, the immunomodulatory effects of the mandible on facial allografts remain unclear. To understand the effects of the mandible on facial allograft survival, we compared the diversities of different facial allograft-elicited alloimmunity between a facial osteomyocutaneous allograft (OMC), including skin, muscle, oral mucosa, and vessels, and especially the mandible, and a myocutaneous allograft (MC) including the skin, muscle, oral mucosa, and vessels, but not the mandible. The different facial allografts of a BALB/c donor were transplanted into a heterotopic neck defect on fully major histocompatibility complex-mismatched C57BL/6 mice. The allogeneic OMC (Allo-OMC) group exhibited significant prolongation of facial allograft survival compared to the allogeneic MC group, both in the presence and absence of FK506 immunosuppressive drugs. With the use of FK506 monotherapy (2 mg/kg) for 21 days, the allo-OMC group, including the mandible, showed prolongation of facial allograft survival of up to 65 days, whereas the myocutaneous allograft, without the mandible, only survived for 34 days. The Allo-OMC group also displayed decreased lymphocyte infiltration into the facial allograft. Both groups showed similar percentages of B cells, T cells, natural killer cells, macrophages, and dendritic cells in the blood, spleen, and lymph nodes. However, a decrease in pro-inflammatory T helper 1 cells and an increase in anti-inflammatory regulatory T cells were observed in the blood and lymph nodes of the Allo-OMC group. Significantly increased percentages of donor immune cells were also observed in three lymphoid organs of the Allo-OMC group, suggesting mixed chimerism induction. These results indicated that the mandible has the potential to induce anti-inflammatory effects and mixed chimerism for prolonging facial allograft survival. The immunomodulatory understanding of the mandible could contribute to reducing the use of immunosuppressive regimens in clinical face allotransplantation including the mandible. View Full-Text
Keywords: vascularized composite allotransplantation; facial transplantation; mice; mandible; regulatory T cells; mixed chimerism vascularized composite allotransplantation; facial transplantation; mice; mandible; regulatory T cells; mixed chimerism
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MDPI and ACS Style

De Paz, D.; Aviña, A.E.; Cardona, E.; Lee, C.-M.; Lin, C.-H.; Lin, C.-H.; Wei, F.-C.; Wang, A.Y.L. The Mandible Ameliorates Facial Allograft Rejection and Is Associated with the Development of Regulatory T Cells and Mixed Chimerism. Int. J. Mol. Sci. 2021, 22, 11104. https://doi.org/10.3390/ijms222011104

AMA Style

De Paz D, Aviña AE, Cardona E, Lee C-M, Lin C-H, Lin C-H, Wei F-C, Wang AYL. The Mandible Ameliorates Facial Allograft Rejection and Is Associated with the Development of Regulatory T Cells and Mixed Chimerism. International Journal of Molecular Sciences. 2021; 22(20):11104. https://doi.org/10.3390/ijms222011104

Chicago/Turabian Style

De Paz, Dante, Ana E. Aviña, Esteban Cardona, Chin-Ming Lee, Chia-Hsien Lin, Cheng-Hung Lin, Fu-Chan Wei, and Aline Y.L. Wang 2021. "The Mandible Ameliorates Facial Allograft Rejection and Is Associated with the Development of Regulatory T Cells and Mixed Chimerism" International Journal of Molecular Sciences 22, no. 20: 11104. https://doi.org/10.3390/ijms222011104

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