The effectiveness and safety of intrauterine infusion of autologous regulatory T cells (Tregs) in patients with recurrent pregnancy loss and low levels of endometrial FoxP3+ cells: A retrospective cohort study
Songchen Cai
Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
Search for more papers by this authorSu Dai
Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
Search for more papers by this authorRong Lin
Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
Search for more papers by this authorChunyu Huang
Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
Search for more papers by this authorYong Zeng
Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
Search for more papers by this authorCorresponding Author
Lianghui Diao
Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
Correspondence
Ruochun Lian, and Lianghui Diao, Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, No. 1001, Fuqiang Road, Futian District, Shenzhen 518045, Guangdong Province, PR China.
Email: [email protected]; [email protected]
Wenwei Tu, the Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, The University of Hong Kong.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Ruochun Lian
Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
Correspondence
Ruochun Lian, and Lianghui Diao, Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, No. 1001, Fuqiang Road, Futian District, Shenzhen 518045, Guangdong Province, PR China.
Email: [email protected]; [email protected]
Wenwei Tu, the Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, The University of Hong Kong.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Wenwei Tu
Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China
Correspondence
Ruochun Lian, and Lianghui Diao, Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, No. 1001, Fuqiang Road, Futian District, Shenzhen 518045, Guangdong Province, PR China.
Email: [email protected]; [email protected]
Wenwei Tu, the Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, The University of Hong Kong.
Email: [email protected]
Search for more papers by this authorSongchen Cai
Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
Search for more papers by this authorSu Dai
Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
Search for more papers by this authorRong Lin
Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
Search for more papers by this authorChunyu Huang
Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
Search for more papers by this authorYong Zeng
Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
Search for more papers by this authorCorresponding Author
Lianghui Diao
Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
Correspondence
Ruochun Lian, and Lianghui Diao, Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, No. 1001, Fuqiang Road, Futian District, Shenzhen 518045, Guangdong Province, PR China.
Email: [email protected]; [email protected]
Wenwei Tu, the Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, The University of Hong Kong.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Ruochun Lian
Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
Correspondence
Ruochun Lian, and Lianghui Diao, Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, No. 1001, Fuqiang Road, Futian District, Shenzhen 518045, Guangdong Province, PR China.
Email: [email protected]; [email protected]
Wenwei Tu, the Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, The University of Hong Kong.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Wenwei Tu
Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China
Correspondence
Ruochun Lian, and Lianghui Diao, Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, No. 1001, Fuqiang Road, Futian District, Shenzhen 518045, Guangdong Province, PR China.
Email: [email protected]; [email protected]
Wenwei Tu, the Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, The University of Hong Kong.
Email: [email protected]
Search for more papers by this authorSongchen Cai and Su Dai contributed equally to this work.
Lianghui Diao, Wenwei Tu and Ruochun Lian jointlysupervised the study.
Abstract
Problem
Regulatory T cells (Tregs) are a specialized type of T cells that help maintain immune tolerance and homeostasis. The potential of Tregs cell-based therapies in treating diseases has been demonstrated in several clinical trials, which have shown promising outcomes and high safety in autoimmune diseases, transplant rejection, and graft-versus-host disease. However, their effectiveness and safety in improving endometrial receptivity and reducing pregnancy loss in human reproduction are unknown.
Method of study
The study used a retrospective design and included patients with recurrent pregnancy loss (RPL) and lower levels of endometrial FoxP3+ Tregs. Patients in the Tregs group (n = 33) received intrauterine Tregs infusion three times during the follicular phase, while the control group (n = 28) did not receive any intrauterine infusion.
Results
The intrauterine infusion of autologous Tregs increased the levels of FoxP3+ Tregs and CD56+ NK cells. Patients in the Treg group had higher live birth rates and lower miscarriage rates, especially early miscarriage rates. However, the two groups had no differences in the implantation rate, clinical pregnancy rate, and percentage of preterm delivery.
Conclusions
The findings suggest that intrauterine Tregs infusion may be a potential therapeutic approach for RPL. Further research in larger clinical trials is needed to confirm these findings.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| aji13735-sup-0001-SuppMat.docx620.6 KB | Supplementary Table S1. Sources of antibodies used in this study. Supplementary Table S2. The endometrial immune profiles of patients in the control and Tregs group before treatment Figure S1. Flowchart detailing the inclusion and exclusion criteria of patients in this study Figure S2. A representative picture of Tregs purity after in vitro expansion |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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