Lactobacillus acidophilus Supplementation Exerts a Synergistic Effect on Tacrolimus Efficacy by Modulating Th17/Treg Balance in Lupus-Prone Mice via the SIGNR3 Pathway
ObjectiveTacrolimus (Tac) is an immunosuppressant used in the treatment of systemic lupus erythematosus (SLE); however, it induces T cell subset imbalances by reducing regulatory T (Treg) cells. Lactobacillus acidophilus (LA) is reported to have therapeutic efficacy in immune-mediated diseases via T...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-12-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.696074/full |
| _version_ | 1818701780406501376 |
|---|---|
| author | Da Som Kim Da Som Kim Da Som Kim Youngjae Park Jeong-Won Choi Jeong-Won Choi Sung-Hwan Park Sung-Hwan Park Mi-La Cho Mi-La Cho Mi-La Cho Seung-Ki Kwok Seung-Ki Kwok |
| author_facet | Da Som Kim Da Som Kim Da Som Kim Youngjae Park Jeong-Won Choi Jeong-Won Choi Sung-Hwan Park Sung-Hwan Park Mi-La Cho Mi-La Cho Mi-La Cho Seung-Ki Kwok Seung-Ki Kwok |
| author_sort | Da Som Kim |
| collection | DOAJ |
| description | ObjectiveTacrolimus (Tac) is an immunosuppressant used in the treatment of systemic lupus erythematosus (SLE); however, it induces T cell subset imbalances by reducing regulatory T (Treg) cells. Lactobacillus acidophilus (LA) is reported to have therapeutic efficacy in immune-mediated diseases via T cell regulation.MethodsThis study investigated whether a combination therapy of LA and Tac improves the therapeutic efficacy of Tac by modulating T cell subset populations in an animal model of SLE. Eight-week-old MRL/lpr mice were orally administered with 5 mg/kg of Tac and/or 50 mg/kg of LA daily for 8 weeks. Cecal microbiota compositions, serum autoantibodies levels, the degree of proteinuria, histological changes in the kidney, and populations of various T cell subsets in the spleen were analyzed.ResultsMice presented with significant gut dysbiosis, which were subsequently recovered by the combination treatment of Tac and LA. Double negative T cells in the peripheral blood and spleens of MRL/lpr mice were significantly decreased by the combination therapy. The combination treatment reduced serum levels of anti-dsDNA antibodies and Immunoglobulin G2a, and renal pathology scores were also markedly alleviated. The combination therapy induced Treg cells and decreased T helper 17 (Th17) cells both in vitro and in vivo. In vitro treatment with LA induced the production of indoleamine-2,3-dioxygenase, programmed death-ligand 1, and interleukin-10 via the specific intracellular adhesion molecule-3 grabbing non-integrin homolog-related 3 receptor signals.ConclusionThe present findings indicate that LA augments the therapeutic effect of Tac and modulates Th17/Treg balance in a murine model of SLE. |
| first_indexed | 2024-12-17T15:26:17Z |
| format | Article |
| id | doaj.art-3d4e450fd3e04c84b5fd784a97b74fab |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T15:26:17Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3d4e450fd3e04c84b5fd784a97b74fab2022-12-21T21:43:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-12-011210.3389/fimmu.2021.696074696074Lactobacillus acidophilus Supplementation Exerts a Synergistic Effect on Tacrolimus Efficacy by Modulating Th17/Treg Balance in Lupus-Prone Mice via the SIGNR3 PathwayDa Som Kim0Da Som Kim1Da Som Kim2Youngjae Park3Jeong-Won Choi4Jeong-Won Choi5Sung-Hwan Park6Sung-Hwan Park7Mi-La Cho8Mi-La Cho9Mi-La Cho10Seung-Ki Kwok11Seung-Ki Kwok12The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaLaboratory of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDepartment of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDivision of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaLaboratory of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDivision of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaLaboratory of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDepartment of Medical Lifescience, College of Medicine, The Catholic University of Korea, Seoul, South KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDivision of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South KoreaObjectiveTacrolimus (Tac) is an immunosuppressant used in the treatment of systemic lupus erythematosus (SLE); however, it induces T cell subset imbalances by reducing regulatory T (Treg) cells. Lactobacillus acidophilus (LA) is reported to have therapeutic efficacy in immune-mediated diseases via T cell regulation.MethodsThis study investigated whether a combination therapy of LA and Tac improves the therapeutic efficacy of Tac by modulating T cell subset populations in an animal model of SLE. Eight-week-old MRL/lpr mice were orally administered with 5 mg/kg of Tac and/or 50 mg/kg of LA daily for 8 weeks. Cecal microbiota compositions, serum autoantibodies levels, the degree of proteinuria, histological changes in the kidney, and populations of various T cell subsets in the spleen were analyzed.ResultsMice presented with significant gut dysbiosis, which were subsequently recovered by the combination treatment of Tac and LA. Double negative T cells in the peripheral blood and spleens of MRL/lpr mice were significantly decreased by the combination therapy. The combination treatment reduced serum levels of anti-dsDNA antibodies and Immunoglobulin G2a, and renal pathology scores were also markedly alleviated. The combination therapy induced Treg cells and decreased T helper 17 (Th17) cells both in vitro and in vivo. In vitro treatment with LA induced the production of indoleamine-2,3-dioxygenase, programmed death-ligand 1, and interleukin-10 via the specific intracellular adhesion molecule-3 grabbing non-integrin homolog-related 3 receptor signals.ConclusionThe present findings indicate that LA augments the therapeutic effect of Tac and modulates Th17/Treg balance in a murine model of SLE.https://www.frontiersin.org/articles/10.3389/fimmu.2021.696074/fullsystemic lupus erythematosusgut microbiomeTacrolimusLactobacillus acidophilusT helper 17 cellregulatory T cell |
| spellingShingle | Da Som Kim Da Som Kim Da Som Kim Youngjae Park Jeong-Won Choi Jeong-Won Choi Sung-Hwan Park Sung-Hwan Park Mi-La Cho Mi-La Cho Mi-La Cho Seung-Ki Kwok Seung-Ki Kwok Lactobacillus acidophilus Supplementation Exerts a Synergistic Effect on Tacrolimus Efficacy by Modulating Th17/Treg Balance in Lupus-Prone Mice via the SIGNR3 Pathway Frontiers in Immunology systemic lupus erythematosus gut microbiome Tacrolimus Lactobacillus acidophilus T helper 17 cell regulatory T cell |
| title | Lactobacillus acidophilus Supplementation Exerts a Synergistic Effect on Tacrolimus Efficacy by Modulating Th17/Treg Balance in Lupus-Prone Mice via the SIGNR3 Pathway |
| title_full | Lactobacillus acidophilus Supplementation Exerts a Synergistic Effect on Tacrolimus Efficacy by Modulating Th17/Treg Balance in Lupus-Prone Mice via the SIGNR3 Pathway |
| title_fullStr | Lactobacillus acidophilus Supplementation Exerts a Synergistic Effect on Tacrolimus Efficacy by Modulating Th17/Treg Balance in Lupus-Prone Mice via the SIGNR3 Pathway |
| title_full_unstemmed | Lactobacillus acidophilus Supplementation Exerts a Synergistic Effect on Tacrolimus Efficacy by Modulating Th17/Treg Balance in Lupus-Prone Mice via the SIGNR3 Pathway |
| title_short | Lactobacillus acidophilus Supplementation Exerts a Synergistic Effect on Tacrolimus Efficacy by Modulating Th17/Treg Balance in Lupus-Prone Mice via the SIGNR3 Pathway |
| title_sort | lactobacillus acidophilus supplementation exerts a synergistic effect on tacrolimus efficacy by modulating th17 treg balance in lupus prone mice via the signr3 pathway |
| topic | systemic lupus erythematosus gut microbiome Tacrolimus Lactobacillus acidophilus T helper 17 cell regulatory T cell |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.696074/full |
| work_keys_str_mv | AT dasomkim lactobacillusacidophilussupplementationexertsasynergisticeffectontacrolimusefficacybymodulatingth17tregbalanceinlupuspronemiceviathesignr3pathway AT dasomkim lactobacillusacidophilussupplementationexertsasynergisticeffectontacrolimusefficacybymodulatingth17tregbalanceinlupuspronemiceviathesignr3pathway AT dasomkim lactobacillusacidophilussupplementationexertsasynergisticeffectontacrolimusefficacybymodulatingth17tregbalanceinlupuspronemiceviathesignr3pathway AT youngjaepark lactobacillusacidophilussupplementationexertsasynergisticeffectontacrolimusefficacybymodulatingth17tregbalanceinlupuspronemiceviathesignr3pathway AT jeongwonchoi lactobacillusacidophilussupplementationexertsasynergisticeffectontacrolimusefficacybymodulatingth17tregbalanceinlupuspronemiceviathesignr3pathway AT jeongwonchoi lactobacillusacidophilussupplementationexertsasynergisticeffectontacrolimusefficacybymodulatingth17tregbalanceinlupuspronemiceviathesignr3pathway AT sunghwanpark lactobacillusacidophilussupplementationexertsasynergisticeffectontacrolimusefficacybymodulatingth17tregbalanceinlupuspronemiceviathesignr3pathway AT sunghwanpark lactobacillusacidophilussupplementationexertsasynergisticeffectontacrolimusefficacybymodulatingth17tregbalanceinlupuspronemiceviathesignr3pathway AT milacho lactobacillusacidophilussupplementationexertsasynergisticeffectontacrolimusefficacybymodulatingth17tregbalanceinlupuspronemiceviathesignr3pathway AT milacho lactobacillusacidophilussupplementationexertsasynergisticeffectontacrolimusefficacybymodulatingth17tregbalanceinlupuspronemiceviathesignr3pathway AT milacho lactobacillusacidophilussupplementationexertsasynergisticeffectontacrolimusefficacybymodulatingth17tregbalanceinlupuspronemiceviathesignr3pathway AT seungkikwok lactobacillusacidophilussupplementationexertsasynergisticeffectontacrolimusefficacybymodulatingth17tregbalanceinlupuspronemiceviathesignr3pathway AT seungkikwok lactobacillusacidophilussupplementationexertsasynergisticeffectontacrolimusefficacybymodulatingth17tregbalanceinlupuspronemiceviathesignr3pathway |