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Immune Tolerance of Human Dental Pulp-Derived Mesenchymal Stem Cells Mediated by CD4⁺CD25⁺FoxP3⁺ Regulatory T-Cells and Induced by TGF-β1 and IL-10.

 Jong Won Hong  ;  Jung Hyun Lim  ;  Chooryung J. Chung  ;  Tae Jo Kang  ;  Tae Yeon Kim  ;  Young Seok Kim  ;  Tae Suk Roh  ;  Dae Hyun Lew 
 YONSEI MEDICAL JOURNAL, Vol.58(5) : 1031-1039, 2017 
Journal Title
Issue Date
Allografts/immunology ; Animals ; Biomarkers/metabolism ; CD4 Antigens/metabolism* ; Cell Proliferation/drug effects ; Coculture Techniques ; Dental Pulp/cytology* ; Forkhead Transcription Factors/metabolism ; Graft Survival/immunology ; Humans ; Immune Tolerance*/drug effects ; Interleukin-10/pharmacology* ; Interleukin-2 Receptor alpha Subunit/metabolism* ; Lymphocyte Culture Test, Mixed ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/cytology ; Mesenchymal Stromal Cells/immunology* ; Mice, Inbred BALB C ; Real-Time Polymerase Chain Reaction ; Skin Transplantation ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology* ; Transforming Growth Factor beta1/pharmacology*
Dental pulp ; immune tolerance ; mesenchymal stem cell
PURPOSE: Most studies on immune tolerance of mesenchymal stem cells (MSCs) have been performed using MSCs derived from bone marrow, cord blood, or adipose tissue. MSCs also exist in the craniofacial area, specifically in teeth. The purpose of this study was to evaluate the mechanisms of immune tolerance of dental pulp-derived MSC (DP-MSC) in vitro and in vivo. MATERIALS AND METHODS: We isolated DP-MSCs from human dental pulp and co-cultured them with CD4⁺ T-cells. To evaluate the role of cytokines, we blocked TGF-β and IL-10, separately and together, in co-cultured DP-MSCs and CD4⁺ T-cells. We analyzed CD25 and FoxP3 to identify regulatory T-cells (Tregs) by fluorescence-activated cell sorting (FACS) and real-time PCR. We performed alloskin grafts with and without DP-MSC injection in mice. We performed mixed lymphocyte reactions (MLRs) to check immune tolerance. RESULTS: Co-culture of CD4⁺ T-cells with DP-MSCs increased the number of CD4⁺CD25⁺FoxP3⁺ Tregs (p<0.01). TGF-β or/and IL-10 blocking suppressed Treg induction in co-cultured cells (p<0.05). TGF-β1 mRNA levels were higher in co-cultured DP-MSCs and in co-cultured CD4⁺ T-cells than in the respective monocultured cells. However, IL-10 mRNA levels were not different. There was no difference in alloskin graft survival rate and area between the DP-MSC injection group and the non-injection group. Nonetheless, MLR was reduced in the DP-MSC injected group (p<0.05). CONCLUSION: DP-MSCs can modulate immune tolerance by increasing CD4⁺CD25⁺FoxP3⁺ Tregs. TGF-β1 and IL-10 are factors in the immune-tolerance mechanism. Pure DP-MSC therapy may not be an effective treatment for rejection, although it may module immune tolerance in vivo.
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Plastic and Reconstructive Surgery (성형외과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Orthodontics (교정과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Young Seok(김영석) ORCID logo https://orcid.org/0000-0002-0981-2107
Lew, Dae Hyun(유대현)
Chung, Chooryung J.(정주령) ORCID logo https://orcid.org/0000-0001-9399-7193
Hong, Jong Won(홍종원) ORCID logo https://orcid.org/0000-0002-7762-0940
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