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A Special Population of Regulatory T Cells Potentiates Muscle Repair
Open accessAbstract
Long recognized to be potent suppressors of immune responses, Foxp3(+)CD4(+) regulatory T (Treg) cells are being rediscovered as regulators of nonimmunological processes. We describe a phenotypically and functionally distinct population of Treg cells that rapidly accumulated in the acutely injured skeletal muscle of mice, just as invading myeloid-lineage cells switched from a proinflammatory to a proregenerative state. A Treg population of similar phenotype accumulated in muscles of genetically dystrophic mice. Punctual depletion of Treg cells during the repair process prolonged the proinflammatory infiltrate and impaired muscle repair, while treatments that increased or decreased Treg activities diminished or enhanced (respectively) muscle damage in a dystrophy model. Muscle Treg cells expressed the growth factor Amphiregulin, which acted directly on muscle satellite cells in vitro and improved muscle repair in vivo. Thus, Treg cells and their products may provide new therapeutic opportunities for wound repair and muscular dystrophies.
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“Several publications identified the epidermal growth factor receptor ligand amphiregulin as a key factor of tissue Treg cells to maintain homeostasis or induce tissue regeneration in a diverse set of tissues, including lung, muscle, and brain [447, 448].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [447]
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“Together, these studies suggest that Treg cells protect from epithelial cell injury by both interacting with immune cells to suppress inflammation and by producing epithelial growth factors that signal to non-immune cells.”
From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [26]
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“Production of amphiregulin (Areg) by regulatory T (Treg) cells promotes repair after acute tissue injury.”
From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [26]
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“In these settings, Treg cell-derived Areg is notably independent of Treg cell-mediated immunosuppression, and acts on tissue-resident mesenchymal cells and stem cells - not immune cells 25,26,28 .”
From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [26]
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“They have been shown to support tissue homeostasis and regeneration, ranging from regulating metabolic parameters in the adipose tissue to potentiating tissue repair [444-446], e.g., in skeletal muscles [447], lung tissue [448], or brain [449].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [447]
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Cites
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InfluentialInnate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus
Monticelli, L. A., Sonnenberg, G. F., Abt, M. C., Alenghat, T., Ziegler, C. G. K., Doering, T. A., Angelosanto, J., Laidlaw, B. J., Yang, C. Y., Sathaliyawala, T., et al. (2011) · Nature Immunology · doi:10.1038/ni.2131 · Cited by 1,327 · cited 1×
“Areg is an EGF family member known to promote healing and regeneration of multiple tissues, for example intestinal mucosa and lung epithelium (Shao and Sheng, 2010; Monticelli et al., 2011).”
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“Sample processing and data analysis were performed as previously described (Cipolletta et al., 2012).”
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“Both ‘‘flavors’’ of myeloid cell are important for proper muscle repair, and any alteration in the tightly orchestrated scenario wherein each accumulates and functions at the site of injury can be detrimental (Tidball and Villalta, 2010).”
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Functional tendon regeneration is driven by regulatory T cells and IL-33 signaling
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Farini, A., Sitzia, C., Villa, C., Cassani, B., Tripodi, L., Legato, M., Belicchi, M., Bella, P., Lonati, C., Gatti, S., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22305-x · Cited by 18
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Treg-Derived Extracellular Vesicles: Roles in Diseases and Theranostics
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Exploring T Cell Receptor Repertoires in Myocardial Diseases
Ashour, D., Gouge, K. L., Rainer, P. P., Mariotti‐Ferrandiz, E., & Ramos, G. C. (2024) · Circulation Research · doi:10.1161/circresaha.124.323661 · Cited by 17
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In Vitro Generation of Brain Regulatory T Cells by Co-culturing With Astrocytes
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“Skeletal muscle Tregs have also been well studied, and Areg has been shown to be a Treg-derived repair factor for muscle damage (7).”
BackgroundHelminth egg derivatives as proregenerative immunotherapies
Maestas, D. R., Chung, L., Han, J., Wang, X., Sommerfeld, S. D., Kelly, S. H., Moore, E., Nguyen, H. H., Mejías, J. C., Peña, A. N., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2211703120 · Cited by 17
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“This in fl ammatory microenvironment after VML has been previously characterized as having an enduring presence of CD4 + and CD8 + T cells, as well as improper macrophage polarization 6,11,15,21,22 .”
InfluentialSelf-citationA distinct “repair” role of regulatory T cells in fracture healing
Wu, T., Wang, L., Jian, C., Zhang, Z., Zeng, R., Mi, B., Liu, G., Zhang, Y., & Chen, S. (2024) · Frontiers of Medicine · doi:10.1007/s11684-023-1024-8 · Cited by 18
Diversity and function of regulatory T cells in health and autoimmune diseases
Lu, Y., & Man, X. (2025) · Journal of Autoimmunity · doi:10.1016/j.jaut.2025.103357 · Cited by 18
Aging: a portrait from gene expression profile in blood cells
Calabria, E., Mazza, E. M. C., Dyar, K. A., Pogliaghi, S., Bruseghini, P., Morandi, C., Salvagno, G. L., Gelati, M., Guidi, G. C., Bicciato, S., et al. (2016) · Aging · doi:10.18632/aging.101016 · Cited by 17
“…(Tregs) stimulate the regeneration of mouse skeletal muscle by promoting the activation of the muscle stem cells, the so called satellite cells [17], and that the impaired regeneration of mouse skeletal muscle during aging is in part due to the reduced recruitment, proliferation, and retention…”
Circulating Tregs Accumulate in Omental Tumors and Acquire Adipose-Resident Features
Liu, M., Starenki, D., Scharer, C. D., Silva-Sánchez, A., Molina, P. A., Pollock, J. S., Cooper, S. J., Arend, R. C., Rosenberg, A. F., Randall, T. D., et al. (2022) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-21-0880 · Cited by 15
McGee, M. C., Zhang, T., Magazine, N., Islam, R., Carossino, M., & Huang, W. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.984476 · Cited by 17
“For example, a well-described tissue resident Treg cell population in visceral adipose tissue (VAT) can preserve insulin sensitivity and regulate adipocyte metabolism (9–11), while Treg cells accumulate and promote tissue repair upon muscle injury (12).”
BackgroundTranslating Treg Therapy in Humanized Mice
Hahn, S. A., Bellinghausen, I., Trinschek, B., & Becker, C. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00623 · Cited by 18
“Strikingly, beyond their role in immune homeostasis and immune cell regulation, specialized Treg subpopulations also interfere with non-immunological processes such as metabolism (39) and wound healing (36, 40, 41).”
BackgroundAl-Dabbagh, S., McPhee, J., Murgatroyd, C., Butler-Browne, G., Stewart, C., & Al-Shanti, N. (2015) · Physiological Reports · doi:10.14814/phy2.12518 · Cited by 15
“Immune cells play a potent role in muscle regeneration in vivo (Tidball and Villalta 2010; Burzyn et al. 2013), with data suggesting that satellite cells require the interaction with a number of nonmyogenic cell populations to enable regeneration following damage (Cerletti et al. 2008).”
BackgroundInfluentialZhang, C., Li, G., Zhang, F., Zhang, Y., Hong, S., Gao, S., Liu, Y., Du, J., & Li, Y. (2024) · Advanced Science · doi:10.1002/advs.202405299 · Cited by 16
Polyphenols and post-exercise muscle damage: a comprehensive review of literature
Zhang, X., Zhong, Y., & Rajabi, S. (2025) · European journal of medical research · doi:10.1186/s40001-025-02506-6 · Cited by 17
“Neutrophils are typically the first responders, activated by elevated Ca2 + and releasing pro-inflammatory cytokines [52].”
The co-inhibitory receptor TIGIT promotes tissue-protective functions in T cells
Panetti, C., Daetwyler, R., Moncsek, A., Patikas, N., Agrafiotis, A., Tang, A., Andreata, F., Fumagalli, V., Lima, J., Wen, L., et al. (2025) · Nature Immunology · doi:10.1038/s41590-025-02300-w · Cited by 16
“12; Fig.”
InfluentialThe role of regulatory T cells in the acquisition of tolerance to food allergens in children
de Quirós, E. B., Seoane-Reula, E., Alonso‐Lebrero, E., Pion, M., & Correa‐Rocha, R. (2018) · Allergologia et Immunopathologia · doi:10.1016/j.aller.2018.02.002 · Cited by 38
PTX3 Predicts Myocardial Damage and Fibrosis in Duchenne Muscular Dystrophy
Farini, A., Villa, C., Silvestre, D. D., Bella, P., Tripodi, L., Rossi, R., Sitzia, C., Gatti, S., Mauri, P., & Torrente, Y. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00403 · Cited by 16
Kharraz, Y., Lukesova, V., Serrano, A. L., Davison, A., & Muñoz‐Cánoves, P. (2022) · Cytometry Part A · doi:10.1002/cyto.a.24568 · Cited by 16
Role of Regulatory T Cells in Skeletal Muscle Regeneration: A Systematic Review
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“Ablation of Treg cells in dystrophic mice was achieved by anti-CD25 treatment in 2–3-week-old mdx mice before the peak of inflammation [33,39].”
BackgroundInfluentialNano-Immunomodulation: A New Strategy for Skeletal Muscle Diseases and Aging?
Millozzi, F., Papait, A., Bouché, M., Parolini, O., & Palacios, D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021175 · Cited by 16
“These cells are known for their immunoregulatory action due to their ability to release IL-10, TGFβ, and amphiregulin, which has been shown to stimulate the satellite cells’ differentiation without impacting their proliferation [55].”
BackgroundAwad, A. E., Ebrahim, M., Eissa, L. A., & El‐Shishtawy, M. M. (2019) · International Journal of Hematology-Oncology and Stem Cell Research · doi:10.18502/ijhoscr.v13i3.1275 · Cited by 16
Corsi, F., Carotenuto, F., Nardo, P. D., & Teodori, L. (2020) · Nanomaterials · doi:10.3390/nano10101963 · Cited by 17
Kersh, A. E., Sasaki, M., Cooper, L., Kissick, H. T., & Pollack, B. P. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00327 · Cited by 16
“The ability of immune cells including CD4 and CD8 T cells to produce AREG further underscores the expanding appreciation for the role of ErbB/HER ligands in adaptive immune responses including those against tumors (Zaiss et al., 2006; Kwong et al., 2010; Qi et al., 2012; Burzyn et al., 2013).”
BackgroundTreg Cells Survive and Thrive in Inhospitable Environments
Grzes, K. M., Field, C. S., & Pearce, E. J. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.012 · Cited by 16
“…and function in tissues with limited glucose concentrations or high lactate concentrations is reinforced by other studies where Treg cells have been shown to play a crucial role in the repair of renal ischemia-reperfusion injury (Gandolfo et al., 2009) or muscle damage (Burzyn et al., 2013).”
BackgroundRegulatory T Cells: Central Concepts from Ontogeny to Therapy
Khor, B. (2017) · Transfusion Medicine Reviews · doi:10.1016/j.tmrv.2016.07.003 · Cited by 15
“Pioneering studies showing that Tregs in muscle overexpress amphiregulin and promote tissue repair have been buttressed by the finding that Treg-specific ablation of amphiregulin leads to increased tissue damage in an infectious lung injury model independent of Tregsuppressive effects [41,42].”
BackgroundMijnheer, G., Servaas, N. H., Leong, J. Y., Boltjes, A., Spierings, E., Chen, P., Lai, L., Petrelli, A., Vastert, S. J., de Boer, R. J., et al. (2023) · eLife · doi:10.7554/elife.79016 · Cited by 12
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“They also release IL-33, which participates in the activation of muscle Treg cells and the recruitment of circulatory Treg cells, which are genetically and functionally distinct [36].”
BackgroundMyoV: a deep learning-based tool for the automated quantification of muscle fibers
Gu, S., Wen, C., Xiao, Z., Huang, Q., Jiang, Z., Liu, H., Gao, J., Li, J., Sun, C., & Yang, N. (2023) · Briefings in Bioinformatics · doi:10.1093/bib/bbad528 · Cited by 15
“MyoV was utilized to predict the muscle fibers [50–59].”
MethodDas, S., Hilman, M. C., Yang, F., Mourkioti, F., Yang, W., & Cullen, D. K. (2024) · Skeletal Muscle · doi:10.1186/s13395-024-00336-4 · Cited by 15
“Amphiregulin has also been found to be a potent mitogen for neural stem cells [54] while promoting neuronal survival and potentiating muscle repair by facilitating myogenesis and differentiation [55, 56].”
BackgroundAhn, J., Kim, B., Bello, A. B., Moon, J. J., Arai, Y., & Lee, S. (2025) · Tissue Engineering and Regenerative Medicine · doi:10.1007/s13770-024-00690-w · Cited by 15
“Tregs significantly influence regeneration across various tissues, including bone [10], cartilage [11], muscle [12], and skin [13].”
Tang, Q., Ramsköld, D., Kryštůfková, O., Mann, H. F., Wick, C., Dastmalchi, M., Lakshmikanth, T., Chen, Y., Mikeš, J., Alexanderson, H., et al. (2018) · Scandinavian Journal of Immunology · doi:10.1111/sji.12732 · Cited by 15
“The FOXP3 finding is intriguing, given the notion that muscle‐resident FOXP3 cells may produce amphiregulin which may contribute to muscle fibre regeneration.(11) However, the molecular correlation to the clinical improvement observed in the ARTEMIS trial still needs further exploration, and this will be further inves…”
BackgroundThéret, M., Low, M., Rempel, L., Li, F. F., Tung, L. W., Contreras, O., Chang, C.-K., Wu, A., Soliman, H. S., & Rossi, F. M. V. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119482 · Cited by 22
Strategies for advanced particulate bone substitutes regulating the osteo-immune microenvironment
Yang, Y., Chu, C., Xiao, W., Liu, L., Man, Y., Lin, J., & Qu, Y. (2022) · Biomedical Materials · doi:10.1088/1748-605x/ac5572 · Cited by 13
“Regulatory T cells (Tregs) are crucial for maintaining self-tolerance, stopping hyperinflamma-tion and promoting bone regeneration [46], which can promote osteogenic differentiation and inhibit osteoclasts formation.”
Bone Morphogenetic Proteins Shape Treg Cells
Kraj, P. J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.865546 · Cited by 19
Implications of regulatory T cells in non-lymphoid tissue physiology and pathophysiology
Malko, D., Elmzzahi, T., & Beyer, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.954798 · Cited by 15
Clinical Applications of Regulatory T cells in Adoptive Cell Therapies
Marshall, G. P., Cserny, J., Perry, D. J., Yeh, W.-I., Seay, H. R., Elsayed, A. G., Posgai, A. L., & Brusko, T. M. (2018) · Cell and Gene Therapy Insights · doi:10.18609/cgti.2018.042 · Cited by 15
“, amphiregulin [94,95]), and/or site-specific mutagenesis of single nucleotide polymorphism (SNPs) associated with disease risk/pathogenesis specific to the intended application.”
BackgroundRegulatory T Cell-Mediated Tissue Repair
Hong, J., & Kim, B.-S. (2018) · Advances in Experimental Medicine and Biology · doi:10.1007/978-981-13-0445-3_14 · Cited by 16
Updates on Inflammatory Molecular Pathways Mediated by ADAM17 in Autoimmunity
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Type 2 immunity is maintained during cancer-associated adipose tissue wasting
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“Regulatory T cells (Tregs) in AT and muscle express ST2, the receptor for IL-33, and require this IL-33/ST2 axis for their development and maintenance over time [27, 28].”
BackgroundKlaus, T., Wilson, A. S., Fichter, M., Bros, M., Bopp, T., & Grabbe, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076331 · Cited by 14
The amphiregulin/EGFR axis has limited contribution in controlling autoimmune diabetes
Raugh, A., Jing, Y., Bettini, M. L., & Bettini, M. (2023) · Scientific Reports · doi:10.1038/s41598-023-45738-4 · Cited by 13
Proenkephalin-A secreted by renal proximal tubules functions as a brake in kidney regeneration
Liu, C., Liu, X., He, Z., Zhang, J., Tan, X., Yang, W., Zhang, Y., Yu, T., Liao, S., Dai, L., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-42929-5 · Cited by 14
Inflammation‐associated genes: risks and benefits to Foxp3+ regulatory T‐cell function
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“33, 50, 51 Notably, the Gata3-promoting activity of IL-33 is suppressed by IL-23, demonstrating a further way in which IL-23 can act to destabilize the Treg phenotype.”
BackgroundCharacterization of the Inflammatory Response in Dystrophic Muscle Using Flow Cytometry
Kastenschmidt, J. M., Avetyan, I., & Villalta, S. A. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7374-3_4 · Cited by 15
“In addition to expressing CD25, CTLA-4, GITR, and helios, muscle Tregs express exceptionally high levels of ST2, PD-1, and amphiregulin [29].”
BackgroundShou, J., Shi, X., Liu, X., Chen, Y., Chen, P., & Xiao, W. (2021) · Laboratory Investigation · doi:10.1038/s41374-021-00542-4 · Cited by 14
“In addition, compared with the uninjured group, the number of Treg cells increased after PD-1 mice skeletal muscle injury, but there was no significant expression change in specific muscle growth factor AREG [19, 20, 23, 25] secreted by Treg cells, indicating that PD-1 knockout may also affect the function of Treg cel…”
BackgroundResultInfluentialDouglas, B. B., Wei, Y. Q., Li, X., Ferguson, A. A., Hung, L., Pastore, C., Kurtz, J. R., McLachlan, J. B., Nolan, T. J., Lok, J. B., et al. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009709 · Cited by 14
“Though we expected these canonical type 2 and immunomodulatory genes to be highly expressed inHulk-expanded 2W1S-specific CD4+ T cells, to our surprise the most significantly upregulated gene in this population was amphiregulin, an EGFR ligand known to be expressed by both Th2 cells as well as Tregs [25,39].”
BackgroundNicholls, J., Cao, B., Texier, L. L., Xiong, L. Y., Hunter, C. R., Llanes, G. T., Aguliar, E. G., Schroder, W. A., Phipps, S., Lynch, J. P., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.737880 · Cited by 14
Kaplan, A., Altara, R., Eid, A. H., Booz, G. W., & Zouein, F. A. (2016) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000436 · Cited by 14
Sun, K.-T., Cheung, K., Au, S. W., Yeung, S. S., & Yeung, E. W. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00999 · Cited by 14
Stem cells in skeletal muscle growth and regeneration in amniotes and teleosts: Emerging themes
Ruparelia, A. A., Ratnayake, D., & Currie, P. D. (2019) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.365 · Cited by 15
“By ablating this subset of Tregs using a mouse line expressing the diphtheria toxin receptor under the control of Foxp3, the subset was shown to control both immune cell infiltration into the wound site and macrophage phenotypic switching from a pro- to an anti-inflammatory state (Burzyn et al., 2013).”
BackgroundInfluentialTrentesaux, C., Striedinger, K., Pomerantz, J. H., & Klein, O. D. (2020) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2020.01.004 · Cited by 15
Intercellular signaling dynamics from a single cell atlas of the biomaterials response
Cherry, C., Maestas, D. R., Han, J., Andorko, J. I., Cahan, P., Fertig, E. J., Garmire, L. X., & Elisseeff, J. H. (2020) · doi:10.1101/2020.07.24.218537
“Communication between immune and tissue modules is an area of growing interest in tissue repair as demonstrated in immune-satellite signaling in muscle (Burzyn et al., 2013) and lymphatic-stem cell signaling in skin (Gur-Cohen et al.”
BackgroundMuscle Stem Cell Microenvironment and Functions in Muscle Regeneration
Li, W., Chen, M., & Zhang, L. (2025) · Biomolecules · doi:10.3390/biom15060765 · Cited by 13
Wang, S., Wang, L., Lin, J., Wang, M., Li, J., Guo, Q., Jiao, C., Tang, N., Ma, J., Zhang, H., et al. (2025) · Mucosal Immunology · doi:10.1016/j.mucimm.2025.05.008 · Cited by 13
How stem cells respond to infection, inflammation and ageing
Poirier, E. Z. (2025) · Nature reviews. Immunology · doi:10.1038/s41577-025-01203-z · Cited by 13
Lui, J. B., McGinn, L., & Chen, Z. (2016) · Gut Microbes · doi:10.1080/19490976.2015.1117737 · Cited by 14
“line, it should be noted that a previous study showed that CD4 Treg cells in the muscle could induce tissue repair by secreting amphiregulin.(27) We also tested the potential of CI-Treg cells in adoptive cell transfer settings.”
ResultGernoux, G., Guilbaud, M., Devaux, M., Journou, M., Pichard, V., Jaulin, N., Léger, A., Duff, J. L., Deschamps, J., Guiner, C. L., et al. (2021) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2021.02.003 · Cited by 13
Muñoz-Melero, M., & Biswas, M. (2024) · Human Gene Therapy · doi:10.1089/hum.2023.227 · Cited by 14
“16 This therapeutic effect can be enhanced by adoptive transfer of antigen-specific Tregs or by the in vivo expansion of polyclonal Tregs with low-dose IL-2/anti-IL-2 complexes.”
Dendritic Cells and the Establishment of Fetomaternal Tolerance for Successful Human Pregnancy
Mahajan, D., Kumar, T., Rath, P. K., Sahoo, A. K., Mishra, B. P., Kumar, S., Nayak, N. R., & Jena, M. K. (2024) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.2478/aite-2024-0010 · Cited by 14
Ceafalan, L. C., Manole, E., Tănase, C., Codrici, E., Mihai, S., Gonzalez, A., & Popescu, B. O. (2015) · The Anatomical Record · doi:10.1002/ar.23254 · Cited by 13
Gupta, S., Adhikary, S., & Hui, S. P. (2021) · Clinical & Experimental Immunology · doi:10.1111/cei.13661 · Cited by 12
“According to researchers, muscle Tregs secrete the growth factor Amphiregulin, which directly affects muscle satellite cells in vitro and enhances in vivo muscle repair [18].”
BackgroundTrain your T cells: How skeletal muscles and T cells keep each other fit during aging
Slaets, H., Fonteyn, L., Eijnde, B. O., & Hellings, N. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.03.006 · Cited by 12
A Context-Dependent Role for αv Integrins in Regulatory T Cell Accumulation at Sites of Inflammation
Mair, I., Zandee, S., Toor, I. S., Saul, L., McPherson, R. C., Leech, M. D., Smyth, D. J., O’Connor, R. A., Henderson, N. C., & Anderton, S. M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00264 · Cited by 15
The lymphoid cell network in the skin
Tikoo, S., Jain, R., Kurz, A. R. M., & Weninger, W. (2018) · Immunology and Cell Biology · doi:10.1111/imcb.12026 · Cited by 14
“growth factor receptor ligand expressed on epithelial cells and thereby directly facilitating tissue repair.(44,45) Consistent with these observations, Ali et al.”
ResultHollmann, C., Wiese, T., Dennstädt, F., Fink, J., Schneider‐Schaulies, J., & Beyersdorf, N. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02363 · Cited by 13
“Apart from mediating protective immunity and inducing autoimmune diseases causing a substantial amount of morbidity and mortality, T cells have been recognized to play an important role in maintaining or restoring tissue homeostasis after muscle damage (23), myocardial infarction (24–26) or stroke (27).”
BackgroundImmunological Considerations for Retinal Stem Cell Therapy
Kramer, J., Chirco, K. R., & Lamba, D. A. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-28471-8_4 · Cited by 13
Benefits and pathologies associated with the inflammatory response
Singh, P., & Chazaud, B. (2021) · Experimental Cell Research · doi:10.1016/j.yexcr.2021.112905 · Cited by 15
Toward a Paradigm to Distinguish Distinct Functions of FOXP3+ Regulatory T Cells
Weinberg, S. E., & Singer, B. D. (2021) · ImmunoHorizons · doi:10.4049/immunohorizons.2100046 · Cited by 12
Loh, L., Orlicky, D. J., Spengler, A., Domenico, J. M., Klarquist, J. S., Levens, C. L., Celli, S. I., Kofonow, J. M., Robertson, C. E., Lantz, O. J., et al. (2025) · Mucosal Immunology · doi:10.1016/j.mucimm.2025.05.006 · Cited by 15
“Additional scoring with two independent tissue repair gene sets derived from muscle regenerating T regs 65 and lung tissue repair post influenza virus infection 66 , corroborated this finding (Supplementary Fig.”
Transient tissue residency and lymphatic egress define human CD56bright NK cell homeostasis
Niehrs, A., Hertwig, L., Buggert, M., Nordström, I., Statzu, M., Pampena, M. B., Samer, S., Knox, J. J., Strunz, B., Sun, D., et al. (2025) · Nature Immunology · doi:10.1038/s41590-025-02290-9 · Cited by 13
“TR T cells have been previously described to express FOXO3 and AREG, which subsequently mediate tissue repair and adaptive responses 37,38 .”
Traxinger, B. R., Vick, S. C., Davis, A. S. W., Voillet, V., Erickson, J. R., Czartoski, J., Teague, C., Prlic, M., & Lund, J. M. (2022) · Mucosal Immunology · doi:10.1038/s41385-022-00542-7 · Cited by 12
Treg-specific deletion of the phosphatase SHP-1 impairs control of inflammation in vivo
Gu, Q., Tung, K. S. K., & Lorenz, U. M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1139326 · Cited by 11
Morrison, R. A., Brookes, S., Puls, T. J., Cox, A. D., Gao, H., Liu, Y., & Voytik‐Harbin, S. L. (2023) · Biomaterials Science · doi:10.1039/d3bm00091e · Cited by 12
Amphiregulin in infectious diseases: Role, mechanism, and potential therapeutic targets
Hsu, C., Faisal, A., Porras, S., Grillo, I. J. P., Mustafa, M. A., Saadh, M. J., Adil, M., & Zainab, H. A. (2023) · Microbial Pathogenesis · doi:10.1016/j.micpath.2023.106463 · Cited by 13
DeBerge, M., Schroth, S. L., Du, F., Yeap, X. Y., Wang, J.-J., Zhang, Z. J., Ansari, M. J., Scott, E. A., & Thorp, E. B. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2319623121 · Cited by 12
ATF4 drives regulatory T cell functional specification in homeostasis and obesity
Wang, K., Farrell, A., Zhou, E., Qin, H., Zeng, Z., Zhou, K., Rocha, K. C. E., Zhang, D., Wang, G., Atakilit, A., et al. (2025) · Science Immunology · doi:10.1126/sciimmunol.adp7193 · Cited by 13
Accumulation of Skeletal Muscle T Cells and the Repeated Bout Effect in Rats
Deyhle, M. R., Carlisle, M., Sorensen, J. R., Hafen, P. S., JESPERSON, K., Ahmadi, M., Hancock, C. R., & Hyldahl, R. D. (2019) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000002256 · Cited by 12
“Previous studies have shown that Treg cells are particularly enriched in regenerating muscle after traumatic injury (11,36), making up about 20% of the whole T-cell pool at 3 d postinjury (36).”
BackgroundResultSingh, S. S., Chauhan, S. B., Ng, S. S., Corvino, D., Rivera, F. D. L., Engel, J. A., Waddell, N., Mukhopadhay, P., Johnston, R. L., Koufariotis, L. T., et al. (2022) · Clinical & Translational Immunology · doi:10.1002/cti2.1396 · Cited by 12
“30 AREG expressed by muscle-resident Treg cells has been shown to improve muscle repair in vivo and also act directly on muscle satellite cells in vitro to mediate tissue repair.”
The potential for Treg-enhancing therapies in tissue, in particular skeletal muscle, regeneration
Hanna, B. S., Yaghi, O., Langston, P. K., & Mathis, D. J. (2022) · Clinical & Experimental Immunology · doi:10.1093/cei/uxac076 · Cited by 14
Self-citationComplete remission of diabetes with a transient HDAC inhibitor and insulin in streptozotocin mice
Kojima, H., Katagi, M., Okano, J., Nakae, Y., Ohashi, N., Fujino, K., Miyazawa, I., & Nakagawa, T. (2023) · Communications Biology · doi:10.1038/s42003-023-05010-x · Cited by 12
Regulatory T cells in lung disease and transplantation
Lao, P., Chen, J., Tang, L., Zhang, J., Chen, Y., Fang, Y., & Fan, X. (2023) · Bioscience Reports · doi:10.1042/bsr20231331 · Cited by 12
Context- and Tissue-Specific Regulation of Immunity and Tolerance by Regulatory T Cells
Ulges, A., Schmitt, E., Becker, C., & Bopp, T. (2016) · Advances in immunology · doi:10.1016/bs.ai.2016.08.002 · Cited by 12
Giovannelli, G., Giacomazzi, G., Grosemans, H., & Sampaolesi, M. (2018) · Muscle & Nerve · doi:10.1002/mus.26112 · Cited by 12
“Injured skeletal muscles are also colonized by different populations of T cells, including T helper lymphocytes (ThL), which have both anti- and pro-fibrotic roles(18); T cytotoxic lymphocytes (TcL), responsible for inflammatory response (promoting eosinophilia(19) and fibrosis(20,21)); and T regulatory lymphocytes (T…”
BackgroundPai, M., Lei, C.-S., Su, S.-T., Yeh, S., & Hou, Y.-C. (2019) · European Journal of Nutrition · doi:10.1007/s00394-019-01951-4 · Cited by 13
Hierarchical signaling transduction of the immune and muscle cell crosstalk in muscle regeneration.
Yang, W.-J., & Hu, P. (2017) · Cellular Immunology · doi:10.1016/j.cellimm.2017.08.006 · Cited by 12
Beyond the membrane: rethinking EGFR signaling in physiology and cancer
Jendrisek, G., Mesa, D., Conte, A., Malabarba, M. G., & Sigismund, S. (2026) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-06036-6 · Cited by 16
“Notably, AREG is also produced by activated T cells, including Tregs and Th2 cells, where it plays a pivotal role in tissue repair and homeostasis by promoting epithelial regeneration and controlling local inflammation [ 1, 91, 92].”
Cabeza‐Fernández, S., White, J. A., McMurran, C. E., Gomez-Sanchez, J. A., & de la Fuente, A. G. (2022) · Immunology and Cell Biology · doi:10.1111/imcb.12610 · Cited by 12
“Unlike Th1, Th17 and Th9 cells, Tregs have been shown to have proregenerative functions in the CNS, similar to what is seen in other tissues such as muscle.(3) Diphtheria toxin–mediated depletion of Tregs has revealed that Tregs are essential for adequate myelin regeneration in lysolecithin-induced demyelination(60) a…”
ResultGenome-wide analysis of a cellular exercise model based on electrical pulse stimulation
Lee, B., Kim, S., Shin, Y. J., Son, Y. H., Yang, J. W., Lee, S.-M., Yang, Y. R., Lee, K., & Kwon, K. (2022) · Scientific Reports · doi:10.1038/s41598-022-25758-2 · Cited by 12
“In injured mouse skeletal muscle, Areg is induced in regulatory T (Treg) cells and acts directly on muscle satellite cells to enhance muscle repair 44 Areg was increased in remobilized soleus muscle at 10 days after hindlimb immobilization in young rats but not in old rats 45 .”
Florio, F., Vencato, S., Papa, F. T., Libergoli, M., Kheir, E., Ghzaiel, I., Rando, T. A., Torrente, Y., & Biressi, S. (2023) · EMBO Molecular Medicine · doi:10.15252/emmm.202317405 · Cited by 11
“Moreover, a large body of evidence identified various subpopulations of immune cells as crucial mediators of effective muscle repair (Shen et al , 2008; Burzyn et al , 2013; Heredia et al , 2013; Lemos et al , 2015; Liu et al , 2017).”
BackgroundUnraveling the secrets of γδ T cells with single-cell biology
Sagar (2023) · Journal of Leukocyte Biology · doi:10.1093/jleuko/qiad131 · Cited by 10
Metadata
- Authors
- Burzyn, D., Kuswanto, W., Kolodin, D., Shadrach, J. L., Cerletti, M., Jang, Y., Sefik, E., Tan, T. G., Wagers, A. J., Benoist, C., & Mathis, D.
- Affiliations
- Harvard University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Mathis, Diane
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 155
- Issue
- 6
- Pages
- 1282-1295
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3894749
- OpenAlex
- W2151328705
- Cited by
- 1,234
- References
- 35
- Citations by year
- 2026: 98 · 2025: 96 · 2024: 101 · 2023: 103 · 2022: 112 · 2021: 117 · 2020: 106 · 2019: 111 · 2018: 112 · 2017: 100 · 2016: 73 · 2015: 62 · 2014: 41 · 2013: 1
- FWCI
- 26.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- Harvard Stem Cell Institute
- National Institute on Aging (R01AG033053)
- National Heart, Lung, and Blood Institute (U01HL100402)
- National Institute of Allergy and Infectious Diseases (R37AI051530)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK036836, R01DK092541)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Keywords
- regulatory T cells, Foxp3, muscle repair, skeletal muscle injury, muscle regeneration, muscular dystrophy, amphiregulin, satellite cells, myeloid cells, Treg depletion, wound healing
- MeSH terms
- Animals, Glycoproteins, Lymphoid Tissue, Mice, Inbred C57BL, Muscular Dystrophies, Receptors, Antigen, T-Cell, Regeneration, Muscle, Skeletal, Intercellular Signaling Peptides and Proteins, T-Lymphocytes, Regulatory, Mice, Transcriptome, EGF Family of Proteins, Amphiregulin
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