FK506 and Lactobacillus acidophilus ameliorate acute graft-versus-host disease by modulating the T helper 17/regulatory T-cell balance
Abstract Background Graft-versus-host disease (GvHD) is a critical complication after allogeneic hematopoietic stem cell transplantation (HSCT). The immunosuppressants given to patients undergoing allogeneic HSCT disturb the microbiome and the host immune system, potentially leading to dysbiosis and...
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| Format: | Article |
| Language: | English |
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BMC
2022-02-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03303-z |
| _version_ | 1818501147638366208 |
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| author | Jin-Ah Beak Min-Jung Park Se-Young Kim JooYeon Jhun Jin Seok Woo Jeong Won Choi Hyun Sik Na Soon Kyu Lee Jong Young Choi Mi-La Cho |
| author_facet | Jin-Ah Beak Min-Jung Park Se-Young Kim JooYeon Jhun Jin Seok Woo Jeong Won Choi Hyun Sik Na Soon Kyu Lee Jong Young Choi Mi-La Cho |
| author_sort | Jin-Ah Beak |
| collection | DOAJ |
| description | Abstract Background Graft-versus-host disease (GvHD) is a critical complication after allogeneic hematopoietic stem cell transplantation (HSCT). The immunosuppressants given to patients undergoing allogeneic HSCT disturb the microbiome and the host immune system, potentially leading to dysbiosis and inflammation, and may affect immune function and bone marrow transplantation. The intestinal microbiome is a target for the development of novel therapies for GvHD. Lactobacillus species are widely used supplements to induce production of antimicrobial and anti-inflammatory factors. Methods We determined the effect of the combination of Lactobacillus acidophilus and FK506 on GvHD following major histocompatibility complex-mismatched bone marrow transplantation. Results The combination treatment suppressed IFN-γ and IL-17-producing T cell differentiation, but increased Foxp3+Treg differentiation and IL-10 production. Also, the combination treatment and combination treated-induced Treg cells modulated the proliferation of murine alloreactive T cells in vitro. Additionally, the combination treatment upregulated Treg-related genes—Nt5e, Foxp3, Ikzf2, Nrp1 and Itgb8—in murine CD4+-T cells. The combination treatment also alleviated GvHD clinically and histopathologically by controlling the effector T cell and Treg balance in vivo. Moreover, the combination treatment decreased Th17 differentiation significantly and significantly upregulated Foxp3 and IL-10 expression in peripheral blood mononuclear cells from healthy controls and liver transplantation (LT) patients. Conclusions Therefore, the combination of L. acidophilus and FK506 is effective and safe for patients undergoing allogeneic hematopoietic stem cell transplantation. |
| first_indexed | 2024-12-10T20:52:13Z |
| format | Article |
| id | doaj.art-a14672ea588e4011ad1478154cf1ee5e |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-10T20:52:13Z |
| publishDate | 2022-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-a14672ea588e4011ad1478154cf1ee5e2022-12-22T01:34:04ZengBMCJournal of Translational Medicine1479-58762022-02-0120111210.1186/s12967-022-03303-zFK506 and Lactobacillus acidophilus ameliorate acute graft-versus-host disease by modulating the T helper 17/regulatory T-cell balanceJin-Ah Beak0Min-Jung Park1Se-Young Kim2JooYeon Jhun3Jin Seok Woo4Jeong Won Choi5Hyun Sik Na6Soon Kyu Lee7Jong Young Choi8Mi-La Cho9The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of KoreaDivision of Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaDivision of Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of KoreaAbstract Background Graft-versus-host disease (GvHD) is a critical complication after allogeneic hematopoietic stem cell transplantation (HSCT). The immunosuppressants given to patients undergoing allogeneic HSCT disturb the microbiome and the host immune system, potentially leading to dysbiosis and inflammation, and may affect immune function and bone marrow transplantation. The intestinal microbiome is a target for the development of novel therapies for GvHD. Lactobacillus species are widely used supplements to induce production of antimicrobial and anti-inflammatory factors. Methods We determined the effect of the combination of Lactobacillus acidophilus and FK506 on GvHD following major histocompatibility complex-mismatched bone marrow transplantation. Results The combination treatment suppressed IFN-γ and IL-17-producing T cell differentiation, but increased Foxp3+Treg differentiation and IL-10 production. Also, the combination treatment and combination treated-induced Treg cells modulated the proliferation of murine alloreactive T cells in vitro. Additionally, the combination treatment upregulated Treg-related genes—Nt5e, Foxp3, Ikzf2, Nrp1 and Itgb8—in murine CD4+-T cells. The combination treatment also alleviated GvHD clinically and histopathologically by controlling the effector T cell and Treg balance in vivo. Moreover, the combination treatment decreased Th17 differentiation significantly and significantly upregulated Foxp3 and IL-10 expression in peripheral blood mononuclear cells from healthy controls and liver transplantation (LT) patients. Conclusions Therefore, the combination of L. acidophilus and FK506 is effective and safe for patients undergoing allogeneic hematopoietic stem cell transplantation.https://doi.org/10.1186/s12967-022-03303-zL. acidophilusFK506Th17 cellRegulatory T cellAllogeneic responseGvHD |
| spellingShingle | Jin-Ah Beak Min-Jung Park Se-Young Kim JooYeon Jhun Jin Seok Woo Jeong Won Choi Hyun Sik Na Soon Kyu Lee Jong Young Choi Mi-La Cho FK506 and Lactobacillus acidophilus ameliorate acute graft-versus-host disease by modulating the T helper 17/regulatory T-cell balance Journal of Translational Medicine L. acidophilus FK506 Th17 cell Regulatory T cell Allogeneic response GvHD |
| title | FK506 and Lactobacillus acidophilus ameliorate acute graft-versus-host disease by modulating the T helper 17/regulatory T-cell balance |
| title_full | FK506 and Lactobacillus acidophilus ameliorate acute graft-versus-host disease by modulating the T helper 17/regulatory T-cell balance |
| title_fullStr | FK506 and Lactobacillus acidophilus ameliorate acute graft-versus-host disease by modulating the T helper 17/regulatory T-cell balance |
| title_full_unstemmed | FK506 and Lactobacillus acidophilus ameliorate acute graft-versus-host disease by modulating the T helper 17/regulatory T-cell balance |
| title_short | FK506 and Lactobacillus acidophilus ameliorate acute graft-versus-host disease by modulating the T helper 17/regulatory T-cell balance |
| title_sort | fk506 and lactobacillus acidophilus ameliorate acute graft versus host disease by modulating the t helper 17 regulatory t cell balance |
| topic | L. acidophilus FK506 Th17 cell Regulatory T cell Allogeneic response GvHD |
| url | https://doi.org/10.1186/s12967-022-03303-z |
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