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 Judi Chung, Tae Jo Kang, Tae Yeon Kim, Young Seok Kim, Tae Suk Roh, Dae Hyun Lew

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1031-1039
Number of pages9
JournalYonsei medical journal
Volume58
Issue number5
DOIs
Publication statusPublished - 2017 Jan 1

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Dental Pulp
Immune Tolerance
Regulatory T-Lymphocytes
Mesenchymal Stromal Cells
Interleukin-10
T-Lymphocytes
Mixed Lymphocyte Culture Test
Messenger RNA
Injections
Graft Survival
Coculture Techniques
Fetal Blood
Adipose Tissue
Real-Time Polymerase Chain Reaction
Cultured Cells
Tooth
Flow Cytometry
Cell Count
Bone Marrow
Cytokines

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Hong, Jong Won ; Lim, Jung Hyun ; Chung, Chooryung Judi ; Kang, Tae Jo ; Kim, Tae Yeon ; Kim, Young Seok ; Roh, Tae Suk ; Lew, Dae Hyun. / 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 In: Yonsei medical journal. 2017 ; Vol. 58, No. 5. pp. 1031-1039.
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abstract = "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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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 . / Hong, Jong Won; Lim, Jung Hyun; Chung, Chooryung Judi; Kang, Tae Jo; Kim, Tae Yeon; Kim, Young Seok; Roh, Tae Suk; Lew, Dae Hyun.

In: Yonsei medical journal, Vol. 58, No. 5, 01.01.2017, p. 1031-1039.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Hong, Jong Won

AU - Lim, Jung Hyun

AU - Chung, Chooryung Judi

AU - Kang, Tae Jo

AU - Kim, Tae Yeon

AU - Kim, Young Seok

AU - Roh, Tae Suk

AU - Lew, Dae Hyun

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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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