TIGIT-Fc as a Potential Therapeutic Agent for Fetomaternal Tolerance
The perfect synchronization of maternal immune-endocrine mechanisms and those of the fetus is necessary for a successful pregnancy. In this report, decidual immune cells at the maternal-fetal interface were detected that expressed TIGIT (T cell immunoreceptor with Ig and ITIM domains), which is a co...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.649135/full |
| _version_ | 1818859560791703552 |
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| author | Wenyan Fu Renfei Cai Zetong Ma Zetong Ma Tian Li Changhai Lei Changhai Lei Jian Zhao Shi Hu Shi Hu |
| author_facet | Wenyan Fu Renfei Cai Zetong Ma Zetong Ma Tian Li Changhai Lei Changhai Lei Jian Zhao Shi Hu Shi Hu |
| author_sort | Wenyan Fu |
| collection | DOAJ |
| description | The perfect synchronization of maternal immune-endocrine mechanisms and those of the fetus is necessary for a successful pregnancy. In this report, decidual immune cells at the maternal-fetal interface were detected that expressed TIGIT (T cell immunoreceptor with Ig and ITIM domains), which is a co-inhibitory receptor that triggers immunological tolerance. We generated recombinant TIGIT-Fc fusion proteins by linking the extracellular domain of TIGIT and silent Fc fragments. The treatment with TIGIT-Fc of human decidual antigen presenting cells (APCs), the decidual dendritic cells (dDCs), and decidual macrophages (dMϕs) increased the production of interleukin 10 and induced the decidua APCs to powerfully polarize the decidual CD4+ T cells toward a classic TH2 phenotype. We further proposed that Notch signaling shows a pivotal effect on the transcriptional regulation in decidual immune cell subsets. Moreover, the administration of TIGIT-Fc to CBA/J pregnant mice at preimplantation induced CD4+ forkhead box P3+ (Foxp3+) regulatory T cells and tolerogenic dendritic cells and increased pregnancy rates in an abortion-prone animal model stress. The results suggested the therapeutic potential of the TIGIT-Fc fusion protein in reinstating immune tolerance in failing pregnancies. |
| first_indexed | 2024-12-19T09:14:08Z |
| format | Article |
| id | doaj.art-b7c45acae2124ccd8eb1c050d375c983 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T09:14:08Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b7c45acae2124ccd8eb1c050d375c9832022-12-21T20:28:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-03-011210.3389/fimmu.2021.649135649135TIGIT-Fc as a Potential Therapeutic Agent for Fetomaternal ToleranceWenyan Fu0Renfei Cai1Zetong Ma2Zetong Ma3Tian Li4Changhai Lei5Changhai Lei6Jian Zhao7Shi Hu8Shi Hu9Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Biophysics, College of Basic Medical Sciences, Second Military Medical University, Shanghai, ChinaTeam SMMU-China of International Genetically Engineered Machine (iGEM) Competitions, Department of Biophysics, Second Military Medical University, Shanghai, ChinaDepartment of Biophysics, College of Basic Medical Sciences, Second Military Medical University, Shanghai, ChinaDepartment of Biophysics, College of Basic Medical Sciences, Second Military Medical University, Shanghai, ChinaTeam SMMU-China of International Genetically Engineered Machine (iGEM) Competitions, Department of Biophysics, Second Military Medical University, Shanghai, ChinaKOCHKOR Biotech, Inc., Shanghai, ChinaDepartment of Biophysics, College of Basic Medical Sciences, Second Military Medical University, Shanghai, ChinaTeam SMMU-China of International Genetically Engineered Machine (iGEM) Competitions, Department of Biophysics, Second Military Medical University, Shanghai, ChinaThe perfect synchronization of maternal immune-endocrine mechanisms and those of the fetus is necessary for a successful pregnancy. In this report, decidual immune cells at the maternal-fetal interface were detected that expressed TIGIT (T cell immunoreceptor with Ig and ITIM domains), which is a co-inhibitory receptor that triggers immunological tolerance. We generated recombinant TIGIT-Fc fusion proteins by linking the extracellular domain of TIGIT and silent Fc fragments. The treatment with TIGIT-Fc of human decidual antigen presenting cells (APCs), the decidual dendritic cells (dDCs), and decidual macrophages (dMϕs) increased the production of interleukin 10 and induced the decidua APCs to powerfully polarize the decidual CD4+ T cells toward a classic TH2 phenotype. We further proposed that Notch signaling shows a pivotal effect on the transcriptional regulation in decidual immune cell subsets. Moreover, the administration of TIGIT-Fc to CBA/J pregnant mice at preimplantation induced CD4+ forkhead box P3+ (Foxp3+) regulatory T cells and tolerogenic dendritic cells and increased pregnancy rates in an abortion-prone animal model stress. The results suggested the therapeutic potential of the TIGIT-Fc fusion protein in reinstating immune tolerance in failing pregnancies.https://www.frontiersin.org/articles/10.3389/fimmu.2021.649135/fullTIGITtargeted therapyfetomaternal toleranceRASIgG based therapy |
| spellingShingle | Wenyan Fu Renfei Cai Zetong Ma Zetong Ma Tian Li Changhai Lei Changhai Lei Jian Zhao Shi Hu Shi Hu TIGIT-Fc as a Potential Therapeutic Agent for Fetomaternal Tolerance Frontiers in Immunology TIGIT targeted therapy fetomaternal tolerance RAS IgG based therapy |
| title | TIGIT-Fc as a Potential Therapeutic Agent for Fetomaternal Tolerance |
| title_full | TIGIT-Fc as a Potential Therapeutic Agent for Fetomaternal Tolerance |
| title_fullStr | TIGIT-Fc as a Potential Therapeutic Agent for Fetomaternal Tolerance |
| title_full_unstemmed | TIGIT-Fc as a Potential Therapeutic Agent for Fetomaternal Tolerance |
| title_short | TIGIT-Fc as a Potential Therapeutic Agent for Fetomaternal Tolerance |
| title_sort | tigit fc as a potential therapeutic agent for fetomaternal tolerance |
| topic | TIGIT targeted therapy fetomaternal tolerance RAS IgG based therapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.649135/full |
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