Dysfunction of Foxp3<sup>+</sup> Regulatory T Cells Induces Dysbiosis of Gut Microbiota via Aberrant Binding of Immunoglobulins to Microbes in the Intestinal Lumen
Foxp3<sup>+</sup> regulatory T (Treg) cells prevent excessive immune responses against dietary antigens and commensal bacteria in the intestine. Moreover, Treg cells contribute to the establishment of a symbiotic relationship between the host and gut microbes, partly through immunoglobul...
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2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| author | Kouhei Koshida Mitsuki Ito Kyosuke Yakabe Yoshimitsu Takahashi Yuki Tai Ryouhei Akasako Tatsuki Kimizuka Shunsuke Takano Natsumi Sakamoto Kei Haniuda Shuhei Ogawa Shunsuke Kimura Yun-Gi Kim Koji Hase Yohsuke Harada |
| author_facet | Kouhei Koshida Mitsuki Ito Kyosuke Yakabe Yoshimitsu Takahashi Yuki Tai Ryouhei Akasako Tatsuki Kimizuka Shunsuke Takano Natsumi Sakamoto Kei Haniuda Shuhei Ogawa Shunsuke Kimura Yun-Gi Kim Koji Hase Yohsuke Harada |
| author_sort | Kouhei Koshida |
| collection | DOAJ |
| description | Foxp3<sup>+</sup> regulatory T (Treg) cells prevent excessive immune responses against dietary antigens and commensal bacteria in the intestine. Moreover, Treg cells contribute to the establishment of a symbiotic relationship between the host and gut microbes, partly through immunoglobulin A. However, the mechanism by which Treg cell dysfunction disturbs the balanced intestinal microbiota remains unclear. In this study, we used Foxp3 conditional knockout mice to conditionally ablate the <i>Foxp3</i> gene in adult mice and examine the relationship between Treg cells and intestinal bacterial communities. Deletion of <i>Foxp3</i> reduced the relative abundance of Clostridia, suggesting that Treg cells have a role in maintaining Treg-inducing microbes. Additionally, the knockout increased the levels of fecal immunoglobulins and immunoglobulin-coated bacteria. This increase was due to immunoglobulin leakage into the gut lumen as a result of loss of mucosal integrity, which is dependent on the gut microbiota. Our findings suggest that Treg cell dysfunction leads to gut dysbiosis via aberrant antibody binding to the intestinal microbes. |
| first_indexed | 2024-03-11T03:40:41Z |
| format | Article |
| id | doaj.art-8c9144fb7ad34182829a62e5c6ecbcfa |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:40:41Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8c9144fb7ad34182829a62e5c6ecbcfa2023-11-18T01:37:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410854910.3390/ijms24108549Dysfunction of Foxp3<sup>+</sup> Regulatory T Cells Induces Dysbiosis of Gut Microbiota via Aberrant Binding of Immunoglobulins to Microbes in the Intestinal LumenKouhei Koshida0Mitsuki Ito1Kyosuke Yakabe2Yoshimitsu Takahashi3Yuki Tai4Ryouhei Akasako5Tatsuki Kimizuka6Shunsuke Takano7Natsumi Sakamoto8Kei Haniuda9Shuhei Ogawa10Shunsuke Kimura11Yun-Gi Kim12Koji Hase13Yohsuke Harada14Laboratory of Pharmaceutical Immunology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, JapanLaboratory of Pharmaceutical Immunology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, JapanDivision of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, JapanLaboratory of Pharmaceutical Immunology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, JapanLaboratory of Pharmaceutical Immunology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, JapanLaboratory of Pharmaceutical Immunology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, JapanDivision of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, JapanDivision of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, JapanLaboratory of Pharmaceutical Immunology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, JapanDepartment of Immunology, University of Toronto, Toronto, ON M5S 1A8, CanadaDivision of Integrated Research, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda 278-0022, JapanDivision of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, JapanResearch Center for Drug Discovery, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, JapanDivision of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, JapanLaboratory of Pharmaceutical Immunology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, JapanFoxp3<sup>+</sup> regulatory T (Treg) cells prevent excessive immune responses against dietary antigens and commensal bacteria in the intestine. Moreover, Treg cells contribute to the establishment of a symbiotic relationship between the host and gut microbes, partly through immunoglobulin A. However, the mechanism by which Treg cell dysfunction disturbs the balanced intestinal microbiota remains unclear. In this study, we used Foxp3 conditional knockout mice to conditionally ablate the <i>Foxp3</i> gene in adult mice and examine the relationship between Treg cells and intestinal bacterial communities. Deletion of <i>Foxp3</i> reduced the relative abundance of Clostridia, suggesting that Treg cells have a role in maintaining Treg-inducing microbes. Additionally, the knockout increased the levels of fecal immunoglobulins and immunoglobulin-coated bacteria. This increase was due to immunoglobulin leakage into the gut lumen as a result of loss of mucosal integrity, which is dependent on the gut microbiota. Our findings suggest that Treg cell dysfunction leads to gut dysbiosis via aberrant antibody binding to the intestinal microbes.https://www.mdpi.com/1422-0067/24/10/8549Foxp3<sup>+</sup> regulatory T cellgut microbiotaimmunoglobulin Gimmunoglobulin Ahelper T cell |
| spellingShingle | Kouhei Koshida Mitsuki Ito Kyosuke Yakabe Yoshimitsu Takahashi Yuki Tai Ryouhei Akasako Tatsuki Kimizuka Shunsuke Takano Natsumi Sakamoto Kei Haniuda Shuhei Ogawa Shunsuke Kimura Yun-Gi Kim Koji Hase Yohsuke Harada Dysfunction of Foxp3<sup>+</sup> Regulatory T Cells Induces Dysbiosis of Gut Microbiota via Aberrant Binding of Immunoglobulins to Microbes in the Intestinal Lumen International Journal of Molecular Sciences Foxp3<sup>+</sup> regulatory T cell gut microbiota immunoglobulin G immunoglobulin A helper T cell |
| title | Dysfunction of Foxp3<sup>+</sup> Regulatory T Cells Induces Dysbiosis of Gut Microbiota via Aberrant Binding of Immunoglobulins to Microbes in the Intestinal Lumen |
| title_full | Dysfunction of Foxp3<sup>+</sup> Regulatory T Cells Induces Dysbiosis of Gut Microbiota via Aberrant Binding of Immunoglobulins to Microbes in the Intestinal Lumen |
| title_fullStr | Dysfunction of Foxp3<sup>+</sup> Regulatory T Cells Induces Dysbiosis of Gut Microbiota via Aberrant Binding of Immunoglobulins to Microbes in the Intestinal Lumen |
| title_full_unstemmed | Dysfunction of Foxp3<sup>+</sup> Regulatory T Cells Induces Dysbiosis of Gut Microbiota via Aberrant Binding of Immunoglobulins to Microbes in the Intestinal Lumen |
| title_short | Dysfunction of Foxp3<sup>+</sup> Regulatory T Cells Induces Dysbiosis of Gut Microbiota via Aberrant Binding of Immunoglobulins to Microbes in the Intestinal Lumen |
| title_sort | dysfunction of foxp3 sup sup regulatory t cells induces dysbiosis of gut microbiota via aberrant binding of immunoglobulins to microbes in the intestinal lumen |
| topic | Foxp3<sup>+</sup> regulatory T cell gut microbiota immunoglobulin G immunoglobulin A helper T cell |
| url | https://www.mdpi.com/1422-0067/24/10/8549 |
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