---
title: "Regulatory T Cell Induction Strategies and Therapeutic Applications in Immune and Non‑Immune Disea"
id: "pubmed-42675035"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42675035"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42675035/"
doi: "10.1038/s41392-026-02910-2"
published_at: "2026-09-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Regulatory T Cell Induction Strategies and Therapeutic Applications in Immune and Non‑Immune Disea
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42675035
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42675035/)
- **DOI:** [10.1038/s41392-026-02910-2](https://doi.org/10.1038%2Fs41392-026-02910-2)
- **Published At:** 2026-09-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- **Regulatory T cells (Treg cells)** are central immune regulators that suppress excessive immune responses and maintain self-tolerance through both contact-dependent and contact-independent mechanisms. - The reviewed induction strategies for Treg cells include **antigenic stimulation**, **cytokine modulation**, manipulation of **metabolic pathways**, **epigenetic regulation**, pharmacologic or **drug induction**, and **engineered technologies**. - Each induction approach offers distinct advantages but none alone fully solves issues of **Treg stability**, **target specificity**, and scalable production for therapy. - The authors advocate integrating multiple induction strategies during Treg generation to improve functionality and broaden clinical applicability of Treg cell therapies. - Therapeutic applications discussed include immune diseases (autoimmune disease, organ transplantation, allergic asthma, cancer) and non-immune conditions (insulin resistance, tissue repair, fibrotic diseases, osteoporosis). - Recent advances and ongoing research bottlenecks are summarized, with emphasis on overcoming current limitations to advance **Treg-based cellular therapies**. - The review aims to deepen mechanistic understanding of Treg biology and provide direction for future development of next-generation Treg therapeutics. - The authors declare no competing interests.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 School of Pharmacy, Zhejiang University, Hangzhou, Zhejiang, PR China. * 2 Zhejiang Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Senile Chronic Diseases, Department of Geriatrics, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, China. zoe411@zju.edu.cn. * 3 School of Pharmacy, Zhejiang University, Hangzhou, Zhejiang, PR China. youjiandoc@zju.edu.cn. * 4 Department of Obstetrics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. youjiandoc@zju.edu.cn. * 5 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, PR China. youjiandoc@zju.edu.cn. * PMID: **42675035** * DOI: [ 10.1038/s41392-026-02910-2 ](https://doi.org/10.1038/s41392-026-02910-2) Item in Clipboard Review # Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases Yaqi Chen et al. Signal Transduct Target Ther. 2026. Show details Display options Display options Format Abstract PubMed PMID Signal Transduct Target Ther Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Signal+Transduct+Target+Ther%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Signal+Transduct+Target+Ther%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42675035/) . 2026 Sep 1;11(1):356. doi: 10.1038/s41392-026-02910-2. ### Authors [Yaqi Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+Y&cauthor_id=42675035)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42675035/#short-view-affiliation-1 "School of Pharmacy, Zhejiang University, Hangzhou, Zhejiang, PR China."), [Yingying Shi](https://pubmed.ncbi.nlm.nih.gov/?term=Shi+Y&cauthor_id=42675035)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42675035/#short-view-affiliation-2 "Zhejiang Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Senile Chronic Diseases, Department of Geriatrics, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, China. zoe411@zju.edu.cn."), [Jian You](https://pubmed.ncbi.nlm.nih.gov/?term=You+J&cauthor_id=42675035)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42675035/#short-view-affiliation-3 "School of Pharmacy, Zhejiang University, Hangzhou, Zhejiang, PR China. youjiandoc@zju.edu.cn.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42675035/#short-view-affiliation-4 "Department of Obstetrics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. youjiandoc@zju.edu.cn.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42675035/#short-view-affiliation-5 "State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, PR China. youjiandoc@zju.edu.cn.") ### Affiliations * 1 School of Pharmacy, Zhejiang University, Hangzhou, Zhejiang, PR China. * 2 Zhejiang Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Senile Chronic Diseases, Department of Geriatrics, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, China. zoe411@zju.edu.cn. * 3 School of Pharmacy, Zhejiang University, Hangzhou, Zhejiang, PR China. youjiandoc@zju.edu.cn. * 4 Department of Obstetrics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. youjiandoc@zju.edu.cn. * 5 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, PR China. youjiandoc@zju.edu.cn. * PMID: **42675035** * DOI: [ 10.1038/s41392-026-02910-2 ](https://doi.org/10.1038/s41392-026-02910-2) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract As a key regulator of the immune system, regulatory T cells (Treg cells) suppress excessive immune responses and maintain self-tolerance through various immunosuppressive mechanisms, both contact-dependent and contact-independent. They have demonstrated significant therapeutic potential in immune-related diseases and some non-immune diseases. In this paper, we systematically review the induction strategies of Treg cells, covering various aspects including antigenic stimulation, cytokine modulation, metabolic pathways, epigenetic regulation, drug induction, and engineered technology. Although each strategy has its own advantages, no single approach can comprehensively address the complex issues surrounding Treg cell stability, target specificity, and large-scale production. Therefore, we propose that integrating multiple induction strategies during the Treg cell induction process is crucial for designing Treg cell therapies with superior functionality and broader applications, thereby overcoming the current limitations of Treg cell therapies. In addition, we introduce their therapeutic applications in immune diseases (such as autoimmune disease, organ transplantation, allergic asthma, and cancer) and non-immune diseases (such as insulin resistance, tissue repair, fibrotic diseases, and osteoporosis), and recent advancements. We also discuss current research bottlenecks of Treg cell-based therapeutic strategies and provide an outlook on their future development, aiming to deepen the understanding of Treg cells and promote the advancement of Treg cell-based cellular therapeutic strategies. © 2026. The Author(s). [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Competing interests: The authors declare no competing interests. ## Similar articles * [ Regulatory T cells in autoimmune diseases: biological mechanisms, clinical translation, and translational challenges. ](https://pubmed.ncbi.nlm.nih.gov/42661942/) Li J, Pang J, Wu P, Wang E, Zheng SJ, Ruan Q, Liu R.Li J, et al.Front Immunol. 2026 Aug 13;17:1881360. doi: 10.3389/fimmu.2026.1881360. eCollection 2026.Front Immunol. 2026.PMID: 42661942Free PMC article.Review. * [ Regulatory T cells in homeostasis and disease: molecular mechanisms and therapeutic potential. ](https://pubmed.ncbi.nlm.nih.gov/41087343/) Wang L, Liang Y, Zhao C, Ma P, Zeng S, Ju D, Zhao M, Yu M, Shi Y.Wang L, et al.Signal Transduct Target Ther. 2025 Oct 14;10(1):345. doi: 10.1038/s41392-025-02326-4.Signal Transduct Target Ther. 2025.PMID: 41087343Free PMC article.Review. * [ Thymic commitment of regulatory T cells is a pathway of TCR-dependent selection that isolates repertoires undergoing positive or negative selection. ](https://pubmed.ncbi.nlm.nih.gov/15981475/) Coutinho A, Caramalho I, Seixas E, Demengeot J.Coutinho A, et al.Curr Top Microbiol Immunol. 2005;293:43-71. doi: 10.1007/3-540-27702-1_3.Curr Top Microbiol Immunol. 2005.PMID: 15981475Review. * [ Regulatory T cell therapy in autoimmune and immune-mediated diseases: from basic research to clinical practice and future perspectives. ](https://pubmed.ncbi.nlm.nih.gov/42183190/) Duan S, Zhang J, Chen Z, He Y, Zhang Y, Guo H.Duan S, et al.Front Immunol. 2026 May 7;17:1772001. doi: 10.3389/fimmu.2026.1772001. eCollection 2026.Front Immunol. 2026.PMID: 42183190Free PMC article.Review. * [ Next-generation regulatory T cell therapy. ](https://pubmed.ncbi.nlm.nih.gov/31541224/) Ferreira LMR, Muller YD, Bluestone JA, Tang Q.Ferreira LMR, et al.Nat Rev Drug Discov. 2019 Oct;18(10):749-769. doi: 10.1038/s41573-019-0041-4. Epub 2019 Sep 20.Nat Rev Drug Discov. 2019.PMID: 31541224Free PMC article.Review. [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=42675035) ## References 1. 1. Savage, P. A., Klawon, D. E. J. & Miller, C. H. Regulatory T cell development. Annu. Rev. Immunol. 38, 421–453 (2020). - [PubMed](https://pubmed.ncbi.nlm.nih.gov/31990619/) - [DOI](https://doi.org/10.1146/annurev-immunol-100219-020937) 2. 1. Nishizuka, Y. & Sakakura, T. Thymus and reproduction: sex-linked dysgenesia of the gonad after neonatal thymectomy in mice. Science 166, 753–755 (1969). - [PubMed](https://pubmed.ncbi.nlm.nih.gov/5823314/) - [DOI](https://doi.org/10.1126/science.166.3906.753) 3. 1. Zhang, H. et al. Cholesterol suppresses human iTreg differentiation and nTreg function through mitochondria-related mechanisms. J. Transl. Med. 21, 224 (2023). - [DOI](https://doi.org/10.1186/s12967-023-03896-z) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/36973679/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/10045251/) 4. 1. van der Veeken, J. et al. Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Treg cells. Immunity 55, 1173–1184.e1177 (2022). - [PubMed](https://pubmed.ncbi.nlm.nih.gov/35700740/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/9885886/) - [DOI](https://doi.org/10.1016/j.immuni.2022.05.010) 5. 1. Bluestone, J. A., McKenzie, B. S., Beilke, J. & Ramsdell, F. Opportunities for Treg cell therapy for the treatment of human disease. Front. Immunol. 14, 1166135 (2023). - [PubMed](https://pubmed.ncbi.nlm.nih.gov/37153574/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/10154599/) - [DOI](https://doi.org/10.3389/fimmu.2023.1166135) Show all 496 references ## Publication types * Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42675035/) ## MeSH terms * Animals Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Animals) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42675035/) * Autoimmune Diseases* / immunology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Autoimmune+Diseases%2Fimmunology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Autoimmune+Diseases) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42675035/) * Autoimmune Diseases* / pathology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Autoimmune+Diseases%2Fpathology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Autoimmune+Diseases) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42675035/) * Autoimmune Diseases* / therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Autoimmune+Diseases%2Ftherapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Autoimmune+Diseases) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42675035/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42675035/) * Neoplasms* / immunology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Neoplasms%2Fimmunology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Neoplasms) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42675035/) * Neoplasms* / therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Neoplasms%2Ftherapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Neoplasms) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42675035/) * T-Lymphocytes, Regulatory* / immunology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22T-Lymphocytes%2C+Regulatory%2Fimmunology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=T-Lymphocytes%2C+Regulatory) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42675035/) * T-Lymphocytes, Regulatory* / transplantation Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22T-Lymphocytes%2C+Regulatory%2Ftransplantation%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search
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