Therapeutic potential of regulatory T cells for stem cell regulation: Insights from Treg-mediated enhancement of limbal stem cell functions

Summary: Regulatory T cells (Tregs) play a key role in immunomodulation and tissue regeneration. Limbal stem cells (LSCs) maintain corneal epithelial homeostasis, and LSC deficiency (LSCD) leads to visual impairment. Current LSCD treatments face donor shortages and graft rejection risks. The present...

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Main Authors: Fei Fang, Tingxi A, Junzhao Chen, Shiding Li, Tianyi Zhou, Liangbo Chen, Yao Fu, Chunyi Shao
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S258900422500776X
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author Fei Fang
Tingxi A
Junzhao Chen
Shiding Li
Tianyi Zhou
Liangbo Chen
Yao Fu
Chunyi Shao
author_facet Fei Fang
Tingxi A
Junzhao Chen
Shiding Li
Tianyi Zhou
Liangbo Chen
Yao Fu
Chunyi Shao
author_sort Fei Fang
collection DOAJ
description Summary: Regulatory T cells (Tregs) play a key role in immunomodulation and tissue regeneration. Limbal stem cells (LSCs) maintain corneal epithelial homeostasis, and LSC deficiency (LSCD) leads to visual impairment. Current LSCD treatments face donor shortages and graft rejection risks. The present study explored Tregs’ therapeutic potential for LSCD in a mouse model of graded LSCD and further explored the direct effect of Tregs on LSCs function by in vitro coculturing human-derived cells. Subconjunctival Tregs injection effectively treated mild and moderate LSCD in mouse models. Coculturing human LSCs with human Tregs promoted LSCs migration, proliferation, and stemness maintenance. Furthermore, amphiregulin (AREG), secreted by Tregs, was crucial to their therapeutic effects, as AREG−/− Tregs resulted in diminished efficacy on LSCD mice compared to wild-type Tregs. These findings highlight Tregs as a promising treatment for LSCD, enhancing LSC function partially via AREG production.
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id doaj-art-2e699e165f5a45f6aca7e6864ecfea7e
institution Kabale University
issn 2589-0042
language English
publishDate 2025-05-01
publisher Elsevier
record_format Article
series iScience
spelling doaj-art-2e699e165f5a45f6aca7e6864ecfea7e2025-08-20T03:48:51ZengElsevieriScience2589-00422025-05-0128511251510.1016/j.isci.2025.112515Therapeutic potential of regulatory T cells for stem cell regulation: Insights from Treg-mediated enhancement of limbal stem cell functionsFei Fang0Tingxi A1Junzhao Chen2Shiding Li3Tianyi Zhou4Liangbo Chen5Yao Fu6Chunyi Shao7Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P.R. China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, P.R. ChinaDepartment of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P.R. China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, P.R. ChinaDepartment of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P.R. China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, P.R. ChinaDepartment of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P.R. China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, P.R. ChinaDepartment of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P.R. China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, P.R. ChinaDepartment of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P.R. China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, P.R. China; Corresponding authorDepartment of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P.R. China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, P.R. China; Corresponding authorDepartment of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P.R. China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, P.R. China; Corresponding authorSummary: Regulatory T cells (Tregs) play a key role in immunomodulation and tissue regeneration. Limbal stem cells (LSCs) maintain corneal epithelial homeostasis, and LSC deficiency (LSCD) leads to visual impairment. Current LSCD treatments face donor shortages and graft rejection risks. The present study explored Tregs’ therapeutic potential for LSCD in a mouse model of graded LSCD and further explored the direct effect of Tregs on LSCs function by in vitro coculturing human-derived cells. Subconjunctival Tregs injection effectively treated mild and moderate LSCD in mouse models. Coculturing human LSCs with human Tregs promoted LSCs migration, proliferation, and stemness maintenance. Furthermore, amphiregulin (AREG), secreted by Tregs, was crucial to their therapeutic effects, as AREG−/− Tregs resulted in diminished efficacy on LSCD mice compared to wild-type Tregs. These findings highlight Tregs as a promising treatment for LSCD, enhancing LSC function partially via AREG production.http://www.sciencedirect.com/science/article/pii/S258900422500776XTherapeuticsImmunologyStem cells research
spellingShingle Fei Fang
Tingxi A
Junzhao Chen
Shiding Li
Tianyi Zhou
Liangbo Chen
Yao Fu
Chunyi Shao
Therapeutic potential of regulatory T cells for stem cell regulation: Insights from Treg-mediated enhancement of limbal stem cell functions
iScience
Therapeutics
Immunology
Stem cells research
title Therapeutic potential of regulatory T cells for stem cell regulation: Insights from Treg-mediated enhancement of limbal stem cell functions
title_full Therapeutic potential of regulatory T cells for stem cell regulation: Insights from Treg-mediated enhancement of limbal stem cell functions
title_fullStr Therapeutic potential of regulatory T cells for stem cell regulation: Insights from Treg-mediated enhancement of limbal stem cell functions
title_full_unstemmed Therapeutic potential of regulatory T cells for stem cell regulation: Insights from Treg-mediated enhancement of limbal stem cell functions
title_short Therapeutic potential of regulatory T cells for stem cell regulation: Insights from Treg-mediated enhancement of limbal stem cell functions
title_sort therapeutic potential of regulatory t cells for stem cell regulation insights from treg mediated enhancement of limbal stem cell functions
topic Therapeutics
Immunology
Stem cells research
url http://www.sciencedirect.com/science/article/pii/S258900422500776X
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