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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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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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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Citations
Cites
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InfluentialFeuerer, M., Herrero, L., Cipolletta, D., Naaz, A., Wong, J., Nayer, A., Lee, J., Goldfine, A. B., Benoist, C., Shoelson, S., et al. (2009) · Nature Medicine · doi:10.1038/nm.2002 · Cited by 2,145 · cited 3×
“However, expression of Egfr was undetectable in Treg cells from lymphoid (spleen, lymph node) or nonlymphoid (muscle, VAT) tissues in our microarray studies.”
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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).”
Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus
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“Sample processing and data analysis were performed as previously described (Cipolletta et al., 2012).”
Self-citationRegulatory interactions between muscle and the immune system during muscle regeneration
Tidball, J. G., & Villalta, S. A. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00735.2009 · Cited by 1,105 · cited 4×
“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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Regulatory T Cells for Control of Autoimmunity
Kawakami, R., & Sakaguchi, S. (2024) · Advances in experimental medicine and biology · doi:10.1007/978-981-99-9781-7_5 · Cited by 13
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Treg derived Amphiregulin protects from murine lupus nephritis via tissue reparative effects
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“Ablation of Foxp3 + cells compromises muscle repair, whereas exogenous amphiregulin administration to Foxp3 + cell-ablated mice was associated with upregulation of muscle repair genes and enhanced myogenic differentiation of satellite cells (30).”
InfluentialRegulatory T Cells in Tumor Microenvironment: Therapeutic Approaches and Clinical Implications
Sureka, N., & Zaheer, S. (2025) · Cell Biology International · doi:10.1002/cbin.70031 · Cited by 13
“Additionally, they are involved in muscle repair (Burzyn et al. 2013), adipocyte function (Feuerer et al. 2009; Cipolletta et al. 2012), and even in regulating retinal inflammation (Deliyanti et al. 2017), highlighting their broad impact on various tissues and organs.”
Liu, O., Xu, J., Wang, F., Jin, W., Zanvit, P., Wang, D., Goldberg, N., Cain, A., Guo, N., Han, Y., et al. (2021) · iScience · doi:10.1016/j.isci.2021.102446 · Cited by 13
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“Although both AREG and HB-EGF are involved in muscle repair processes in mice [21,22], little is known about their roles in IIM.”
BackgroundRegulatory T-cells and IL-5 mediate pain outcomes in a preclinical model of chronic muscle pain
Lenert, M. E., Szabo-Pardi, T. A., & Burton, M. D. (2022) · Molecular Pain · doi:10.1177/17448069221110691 · Cited by 12
“A few studies have shown that T-cell and monocyte interactions in injured muscle tissue promote tissue repair, such that Tregs promote monocyte polarization towards a pro-inflammatory phenotype.(58,59) Th1 pro-inflammatory cells are robust producers of IFN-γ which increases MHC-II expression and antigen presentation b…”
BackgroundThe expanding impact of T-regs in the skin
Hajam, E. Y., Panikulam, P., Chu, C.-C., Jayaprakash, H., Majumdar, A., & Jamora, C. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.983700 · Cited by 11
“Altogether, these observations highlight the importance of cutaneous Tregs as an integral component in maintaining skin immune homeostasis, thereby sustaining a healthy skin barrier function and support/regulating tissue regeneration (Figure 2) The reparative roles of T-regs are not only limited to the skin as it has…”
BackgroundIL-2 availability regulates the tissue specific phenotype of murine intra-hepatic Tregs
Kurt, A., Strobl, K., Ruiz, P., Osborn, G., Chester, T., Dawson, L. N., Warwas, K. M., Grey, E. H., Mastoridis, S., Kodela, E., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1040031 · Cited by 8
Influence of Immune Responses in Gene/Stem Cell Therapies for Muscular Dystrophies
Farini, A., Sitzia, C., Erratico, S., Meregalli, M., & Torrente, Y. (2014) · BioMed Research International · doi:10.1155/2014/818107 · Cited by 12
Temporospatial Analysis and New Players in the Immunology of Amyotrophic Lateral Sclerosis
Iyer, A. K., Jones, K. J., Sanders, V. M., & Walker, C. L. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020631 · Cited by 11
“These cells accumulate around the time when infiltrating myeloid cells switch from proinflammatory to a regenerative phenotype [88].”
BackgroundRegulatory T Cells and Their Clinical Applications in Antitumor Immunotherapy
Xie, F., Liang, R., Li, D., & Li, B. (2018) · Engineering · doi:10.1016/j.eng.2018.12.002 · Cited by 11
Strenzke, M., Alberton, P., Aszódi, A., Docheva, D., Haas, E. M., Kammerlander, C., Böcker, W., & Saller, M. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21061965 · Cited by 12
“However, paracrine signals from non-muscular cells, such as infiltrating regulatory T-cells [8] or macrophages [9], spatiotemporally secret pro- and anti-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, fibroblast growth factor 2 (FGF2), insulin-like growth factor 1 (IGF1) and hepatocyte growth fac…”
BackgroundVitamin D Merging into Immune System-Skeletal Muscle Network: Effects on Human Health
Crescioli, C. (2020) · Applied Sciences · doi:10.3390/app10165592 · Cited by 12
“The interplay satellite-Treg seems to be dependent on IL-33, present in the fibro/adipogenic progenitor-like cells within muscle tissue, and regulated by the protein amphiregulin, a growth factor directly promoting staminal cell growth [54,55].”
BackgroundRe-thinking our understanding of immunity: Robustness in the tissue reconstruction system
Truchetet, M., & Pradeu, T. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2018.02.013 · Cited by 12
Signal control during tissue regeneration in adult animals
Bangru, S., Diegmiller, R., Talia, S. D., & Poss, K. D. (2025) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-025-00917-1 · Cited by 11
The role of the immune system during regeneration of the central nervous system
Sabin, K. Z., & Echeverri, K. (2019) · Journal of Immunology and Regenerative Medicine · doi:10.1016/j.regen.2019.100023 · Cited by 10
Dampening antiviral immunity can protect the host
Panetti, C., Kao, K., & Joller, N. (2021) · FEBS Journal · doi:10.1111/febs.15756 · Cited by 10
Dynamics of tissue repair regulatory T cells and damage in acute Trypanosoma cruzi infection
Boccardo, S., Rodríguez, C., Giménez, C. M. S., Furlan, C. L. A., Abrate, C., Almada, L., Saldivia, M., Skewes-Cox, P., Rao, S. P. S., Mukdsi, J. H., et al. (2025) · PLoS Pathogens · doi:10.1371/journal.ppat.1012906 · Cited by 10
p16High immune cells control disease tolerance as a defense and health span-extending strategy
Triana-Martínez, F., Pierantoni, A., Graça, D., Bergo, V., Emelyanov, A., Gallerand, A., Grosse, L., Grigorash, B. B., Polyzou, A., Castiglione, A., et al. (2026) · Immunity · doi:10.1016/j.immuni.2026.02.013 · Cited by 10
Immunoproteasome Inhibition Ameliorates Aged Dystrophic Mouse Muscle Environment
Tripodi, L., Molinaro, D., Fortunato, F., Mella, C., Cassani, B., Torrente, Y., & Farini, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232314657 · Cited by 10
“Muscles were excised and extensively washed in PBS to remove blood contaminants [59], cut in small pieces and digested for 1 h with liberase 0.”
MethodPattern of cardiotoxin-induced muscle remodeling in distinct TLR-4 deficient mouse strains
Paiva-Oliveira, E. L., da Silva, R. D., Bellio, M., Quirico-Santos, T., & Lagrota-Candido, J. (2017) · Histochemistry and Cell Biology · doi:10.1007/s00418-017-1556-6 · Cited by 9
Geng, S., Zhong, Y., Zhou, X., Zhao, G., Xie, X., Pei, Y., Hu, L., Zhang, H., Shi, Y., & Wang, B. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00663 · Cited by 10
The molecular interplay between progenitors and immune cells in tissue regeneration and homeostasis
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Effects of Blood Flow Restriction on Leukocyte Profile and Muscle Damage
dos Santos, L. R., Andreatta, M. V., Curty, V. M., Marcarini, W., Ferreira, L. G., & Barauna, V. G. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.572040 · Cited by 5
“Burzyn et al. (2013) demonstrated that treatment with AREG normalizes the evolution of the muscle transcriptome throughout the muscle repair process and promotes myogenic differentiation in vitro (Burzyn et al., 2013).”
BackgroundInfluentialSoluble interleukin 2 receptor is risk for sarcopenia in Men with high fracture risk
Ge, J., Zeng, J., Li, N., Ma, H., Zhao, Z., Sun, S., Jing, Y., Qian, C., Fei, Z., Qu, S., et al. (2022) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2022.10.017 · Cited by 10
Ezh2 Lines Up the Chromatin in T Regulatory Cells
Wu, C., Chen, Z., & Kuchroo, V. K. (2015) · Immunity · doi:10.1016/j.immuni.2015.01.019 · Cited by 10
“Moreover, Treg cells change their phenotype and function in different inflammatory conditions and tissue environments and become specialized to mediate their specific effector in defined tissues (Burzyn et al., 2013; Cipolletta et al., 2012).”
BackgroundThe widespread myofascial pain of fibromyalgia is sympathetically maintained and immune mediated
Liptan, G. L. (2023) · Journal of Bodywork and Movement Therapies · doi:10.1016/j.jbmt.2023.04.081 · Cited by 10
Kinin receptors regulate skeletal muscle regeneration: differential effects for B1 and B2 receptors
Martins, L. D. O., Amorim, W. W. D. A. A., Gregnani, M. F., Araújo, R. D. C., Qadri, F., Bäder, M., & Pesquero, J. B. (2023) · Inflammation Research · doi:10.1007/s00011-023-01766-4 · Cited by 9
Running on empty: Exploring stem cell exhaustion in geriatric musculoskeletal disease
Lawton, A., Tripodi, N., & Feehan, J. (2024) · Maturitas · doi:10.1016/j.maturitas.2024.108066 · Cited by 10
Zammit, N. W., Vargas‐Castillo, A., Langston, P. K., Wang, G., Zhou, Y., Spiegelman, B. M., Benoist, C. O., & Mathis, D. J. (2025) · Science Immunology · doi:10.1126/sciimmunol.ads0478 · Cited by 13
Self-citationElizagaray, M. L., Barrachina, F., Avenatti, M. C., Bastepe, I., Chen, A., Larrañaga, A. O., Ukairo, O., Ros, V. G. D., Ottino, K., Subirán, N., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-63514-y · Cited by 9
“A similar amount of Tregs has been observed in non-lymphoid tissues under physiological conditions, including adipose tissue 37 and muscle 38 .”
Saravia, J., Chapman, N. M., Sun, Y., Meng, X., Risch, I., Li, W., Guy, C. S., Shi, H., Hu, H., Dhungana, Y., et al. (2025) · Science Immunology · doi:10.1126/sciimmunol.ads9456 · Cited by 11
Cytokine networks in immune-mediated muscle regeneration
Dziki, J. L., Velayutham, M., Hussey, G. S., & Turnquist, H. R. (2018) · Journal of Immunology and Regenerative Medicine · doi:10.1016/j.regen.2018.03.001 · Cited by 9
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TREG Cells in Cancer: Beyond Classical Immunological Control
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“This observation is particularly interesting, since more abundant cell types in the lung parenchyma also produce AREG, but do not compensate for its specific loss in the TREG-cell compartment.”
BackgroundInfluentialIRF8: identity-keeper for suppressive Th1-like Treg cells
Lee, G. R. (2018) · Cellular and Molecular Immunology · doi:10.1038/s41423-018-0044-9 · Cited by 9
Metabolic adaptation orchestrates tissue context‐dependent behavior in regulatory T cells
Wang, H., Lu, C., & Ho, P. (2020) · Immunological Reviews · doi:10.1111/imr.12844 · Cited by 10
Opstelten, R., & Amsen, D. (2021) · Immunology Letters · doi:10.1016/j.imlet.2021.03.002 · Cited by 9
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Yang, J., Zou, M., Chu, X., Floess, S., Li, Y., Delacher, M., & Huehn, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.991671 · Cited by 11
Stepwise acquisition of unique epigenetic signatures during differentiation of tissue Treg cells
Braband, K. L., Kaufmann, T., Floess, S., Zou, M., Huehn, J., & Delacher, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1082055 · Cited by 10
“Upon muscle damage, however, repairtype Treg cells rapidly accumulate and secrete Areg to boost satellite cell function (37).”
BackgroundRegulatory T-cell–intrinsic amphiregulin is dispensable for suppressive function
Carney, K., Chang, Y., Wilson, S. P., Calnan, C., Reddy, P. S., Chan, W.-Y., Gilmartin, T. J., Hernandez, G. E., Schaffer, L., Head, S. R., et al. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.01.030 · Cited by 9
“Populations of tissue-specific murine CD4(1)Foxp3(1) regulatory T (Treg) cells in the colon and striatedmuscle are enriched in amphiregulin during inflammation; indeed, amphiregulin plays a role in repair functions of muscle Treg cells.(3) Treg cells transferred to amphiregulinRAGmice show suboptimal ability to preven…”
BackgroundMothe‐Satney, I., Piquet, J., Murdaca, J., Sibille, B., Grimaldi, P. A., Neels, J. G., & Rousseau, A. (2016) · Biochimie · doi:10.1016/j.biochi.2016.12.001 · Cited by 9
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Tissue-Resident Lymphocytes: Implications in Immunotherapy for Hepatocellular Carcinoma
Han, J. W., & Yoon, S. K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010232 · Cited by 9
“Tissue-resident Treg cells are well described in visceral adipose tissues [56,57], muscle [58], and skin [59].”
BackgroundReprogramming adult tendon healing using regenerative neonatal regulatory T cellsPreprint
Arvind, V., Howell, K., & Huang, A. H. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.05.12.443424 · Cited by 8
The Role of Immune Cells in Liver Regeneration
Wen, Y. (2023) · Livers · doi:10.3390/livers3030029 · Cited by 8
A link between mitochondrial damage and the immune microenvironment of delayed onset muscle soreness
Li, Z., Peng, L., Sun, L., & Si, J. (2023) · BMC Medical Genomics · doi:10.1186/s12920-023-01621-9 · Cited by 8
“In addition, skeletal muscle can cause T cells to accumulate near growth fibres after injury [36, 38].”
BackgroundMuscle stem cells as immunomodulator during regeneration
Xu, H., Le, V. V., Oprescu, S. N., & Kuang, S. (2024) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2024.01.010 · Cited by 9
Zfp697 is an RNA-binding protein that regulates skeletal muscle inflammation and remodeling
Correia, J. C., Jannig, P. R., Gosztyla, M. L., Červenka, I., Ducommun, S., Præstholm, S. M., Dias, J. M. M., Dumont, K. D., Liu, Z., Liang, Q., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2319724121 · Cited by 11
Ward, S., Crawford, G., Buang, N. B., Malactou, C., Dutton, E. E., Withnell, I., Woollard, K. J., Harwood, C. A., McSorley, H. J., Ziegenhain, C., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115837 · Cited by 8
“Analysis of tissue cross-sections using immunofluorescence confirmed that inflamed skin harbored a large number of FoxP3 + cells in the dermis, as well as some on the other side of the basement membrane localized in close proximity to IL-33 + ECs (Figure 3G).”
InfluentialPark, S.-Y., Son, K., Kim, J., Kim, K., Joo, S., Kim, B., Lee, M., Kim, W., Jung, W.-J., Choi, B. K., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-64500-0 · Cited by 8
“TheimmunosuppressiveTMElimits cytotoxic T cell activity, while chronically in fl amed muscle, normally immune-privileged, becomes permissive to CD8 + T cell in fi ltration 110 – 112 .”
Regulatory T cells in cancer and inflammation
Yang, H., Zhang, H., Xia, N., & Cheng, X. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02584-w · Cited by 8
The adaptability of regulatory T cells and Foxp3
Hori, S., & Murakami, R. (2021) · International Immunology · doi:10.1093/intimm/dxab045 · Cited by 8
Striated muscle: an inadequate soil for cancers
Saunders, A. A. E., Thomson, R. E., Goodman, C. A., Anderson, R. L., & Gregorevic, P. (2024) · Cancer and Metastasis Reviews · doi:10.1007/s10555-024-10199-2 · Cited by 8
“Some evidence suggests that skeletal muscle-resident Tregs display a distinct transcriptomic profile compared to Tregs residing in other organs [89].”
BackgroundSoslow, J. H., Markham, L. W., Burnette, W. B., Galindo, C. L., Feoktistov, I., Raucci, F. J., Damon, B. M., Sawyer, D. B., & Ryzhov, S. V. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00914 · Cited by 8
“In contrast, regulatory T cells (Tregs) produce IL-10 and contribute to muscle regeneration in mdx mice (Burzyn et al., 2013; Villalta et al., 2014).”
BackgroundLAG-3 Represents a Marker of CD4+ T Cells with Regulatory Activity in Patients with Bone Fracture
Wang, J., Ti, Y., Wang, Y., Guo, G., Jiang, H., Chang, M., Qian, H., Zhao, J., & Sun, G. (2018) · Immunological Investigations · doi:10.1080/08820139.2018.1458107 · Cited by 8
“Treg cells can limit the extent of inflammation resulting from trauma, tissue necrosis, and infections, and can promote tissue remodeling by releasing growth factors (Arpaia et al., 2015; Burzyn et al., 2013).”
BackgroundBurzyn, D., Wagers, A., Mathis, D., & Cerletti, M. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-8938-6_16 · Cited by 5
Self-citationCombined methods to evaluate human cells in muscle xenografts
Bensalah, M., Klein, P., Riederer, I., Chaouch, S., Muraine, L., Savino, W., Butler-Browne, G., Trollet, C., Mouly, V., Bigot, A., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0211522 · Cited by 4
Çetin, Ş., Gündüz, A., Çetin, A. Ş., Gürdal, A., Sumerkan, M. C., Yıldız, S. S., Uzun, N., & Kılıçkesmez, K. (2018) · Europe PMC (PubMed Central) · doi:10.6515/acs.201807_34(4).20180222b · Cited by 8
Kakiuchi, M., Hirata, Y., Robson, S. C., & Fujisaki, J. (2020) · Haematologica · doi:10.3324/haematol.2019.221820 · Cited by 8
Advances in Human Immune System Mouse Models for Personalized Treg-Based Immunotherapies
Serr, I., Kral, M., Scherm, M. G., & Daniel, C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.643544 · Cited by 8
Salnikov, L., & Baramiya, M. G. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.655315 · Cited by 9
Distinct Injury Responsive Regulatory T Cells Identified by Multi-Dimensional Phenotyping
Guo, F., Hancock, B. L., Griffith, A. M., Lin, H., Howard, K., Keegan, J., Zhang, F., Chicoine, A. T., Cahill, L. A., Ng, J., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.833100 · Cited by 8
Epithelial cell-derived cytokine TSLP activates regulatory T cells by enhancing fatty acid uptake
Kasuya, T., Tanaka, S., Tamura, J., Etori, K., Shoda, J., Hattori, K., Endo, Y., Kitajima, M., Kageyama, T., Iwamoto, T., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-28987-1 · Cited by 9
Kase, N., Kitagawa, Y., Ikenaka, A., Niwa, A., & Saito, M. K. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1022081 · Cited by 7
“This process results in efficient regeneration because of the potential of satellite cells and their interaction with various cells within the skeletal muscle niche, such as fibro-adipogenic progenitors (Joe et al., 2010; Uezumi et al., 2010), regulatory T-cells (Burzyn et al., 2013; Castiglioni et al., 2015), and mac…”
BackgroundMa, R., Prigge, A. D., Serrano, T. P. O., Cheng, Y., Davis, J. M., Lou, K. F., Wood, W. A., Do, H. C., Ren, Z., Fulcer, M. M., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.115056 · Cited by 8
Feuerer, M., Gray, D. H. D., Rankin, L. C., Schmidleithner, L., & Liston, A. (2026) · Annual Review of Immunology · doi:10.1146/annurev-immunol-082924-092651 · Cited by 8
Regulatory T cells: master orchestrators of immune tolerance and tissue homeostasis
Bluestone, J. A., Levings, M. K., Ramsdell, F. J., Rudensky, A. Y., Tang, Q., & Trzonkowski, P. (2026) · Frontiers in Science · doi:10.3389/fsci.2026.1792210 · Cited by 10
“In models of acute skeletal muscle injury, Tregs activate satellite cells to promote repair in an AREG-dependent manner; when Tregs are depleted, recovery falters and in fl ammation persists (106).”
Temporal static and dynamic imaging of skeletal muscle in vivo
Evano, B., Sarde, L., & Tajbakhsh, S. (2023) · Experimental Cell Research · doi:10.1016/j.yexcr.2023.113484 · Cited by 7
Mechanisms of ferroptosis with immune infiltration and inflammatory response in rotator cuff injury
Tong, Z., Li, H., Jin, Y., Sheng, L., Ying, M., Liu, Q., Wang, C., & Teng, C. (2023) · Genomics · doi:10.1016/j.ygeno.2023.110645 · Cited by 7
The effect of PDK1 in maintaining immune cell development and function
Huang, Y., Feng, Q., Zhang, Y., Zeng, Y., Shi, N., Chen, Y., Tang, X., & Li, Z. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.150106 · Cited by 7
Chen, X., Zhang, D., Chen, X., Meng, G., Zheng, Q., Mai, W., Wu, Y., Ye, L., & Wang, L. (2017) · Vaccine · doi:10.1016/j.vaccine.2017.07.014 · Cited by 7
Unique Tailoring of Th17 at the Gingival Oral Mucosal Barrier
Konkel, J. E., & Moutsopoulos, N. M. (2017) · Journal of Dental Research · doi:10.1177/0022034517736030 · Cited by 7
LIF and multiple sclerosis: One protein with two healing properties
Metcalfe, S. M. (2018) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2018.01.018 · Cited by 7
Rousseau, A., Murdaca, J., Menn, G. L., Sibille, B., Wahli, W., Garf, S. L., Chinetti, G., Neels, J. G., & Mothe‐Satney, I. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.587753 · Cited by 7
“Recent data from the group of D. Mathis have shown that CD4+ T cells present in injured mouse SKM are mainly Tregs, constituting 40 to 60% of the CD4+ T cell compartment (Burzyn et al., 2013; Kuswanto et al., 2016).”
BackgroundMethodResultInfluentialCostly immunometabolic remodelling in disused muscle buildup through physical exercise
Padilha, C. S., Figueiredo, C., Deminice, R., Krüger, K., Seelaender, M. C. L., Neto, J. C. R., & Lira, F. S. (2022) · Acta Physiologica · doi:10.1111/apha.13782 · Cited by 7
Alexander, K. A., Tseng, H., Kulina, I., Fleming, W., Vaquette, C., Genêt, F., Ruitenberg, M. J., & Lévesque, J.-P. (2022) · Neurotrauma Reports · doi:10.1089/neur.2021.0072 · Cited by 7
“Depletion of regulatory T cells has also been shown to impair muscle regeneration because of the prolonged presence of inflammatory cells in damaged muscle that subsequently impaired the regeneration process.(46) However, we did not evaluate muscle repair in our model of”
BackgroundRegulatory T cell niche in the bone marrow, a new player in Haematopoietic stem cell transplantation
Ashman, J., Mutsonziwa, N., Romano, M., Kordasti, S. Y., Lombardi, G., & Shangaris, P. (2022) · Blood Reviews · doi:10.1016/j.blre.2022.101030 · Cited by 9
Chen, Q., Chang, H., Su, Y., Zhao, Q. J., Pu, Y., He, X., Jiang, L., Ma, Y., Zhao, Q., & Ye, S. (2023) · Animals · doi:10.3390/ani13061076 · Cited by 7
Badarinath, K., Dutta, A., Hegde, A., Pincha, N., Gund, R., & Jamora, C. (2018) · Methods in molecular biology · doi:10.1007/7651_2018_155 · Cited by 7
Regulating heart repair with cardiac-specific T lymphocytes
Mallat, Z. (2019) · Journal of Clinical Investigation · doi:10.1172/jci132441 · Cited by 7
Gao, S., Chen, S. N., Nardo, C. D., & Lombardi, R. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00834 · Cited by 8
Langenhorst, D., Tabares, P., Gulde, T., Becklund, B. R., Berr, S., Surh, C. D., Beyersdorf, N., & Hünig, T. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01985 · Cited by 7
Intragraft memory-like CD127hiCD4+Foxp3+ Tregs maintain transplant tolerance
Zhao, Y., Nicholson, L., Wang, H., Yi, Q., Hawthorne, W. J., Jimenez‐Vera, E., Gloss, B., Lai, J., Thomas, A., Chew, Y. V., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.169119 · Cited by 6
“ST2 + tissue Tregs are highly suppressive, are associated with homeostasis and tissue repair function, and are found in a broad range of tissues, including skin, muscle (32), colon/intestine (33, 34), lung (33), brain (35), visceral adipose tissue (6, 33, 36), and kidney (37).”
BackgroundInfluentialCellular Senescence in the Regenerative Niche Hampers Skeletal Muscle Repair
Qiu, M., Li, Y., Wang, Q., Jian, X., Huang, J.-W., Gui, W., Hu, J., & Liao, H. (2025) · Aging and Disease · doi:10.14336/ad.2024.1501 · Cited by 6
“Regulatory T cells (Tregs) critically regulate macrophage polarization dynamics within the niche [11].”
InfluentialEngineering the immune and fibrotic response in VML
Altamirano, D. E., Davis, D., Mao, H., & Grayson, W. L. (2025) · The Journal of Physiology · doi:10.1113/jp286608 · Cited by 6
“However, a specific population of T regs has been shown to respond to chemical injury in skeletal muscle, and increasing T regs activity reduces muscle damage in a dystrophy model of regeneration (Burzyn et al., 2013).”
Beumer, N., Imbusch, C. D., Kaufmann, T., Schmidleithner, L., Guetter, K., Stüve, P., Marchel, H., Weichenhan, D., Bähr, M., Ruhland, B., et al. (2025) · Nature Immunology · doi:10.1038/s41590-025-02210-x · Cited by 6
“49), and work on mouse muscle T reg cells showed shared muscle T reg cell TCR sequences in a specific spleen T reg cell population, compatible with recirculating muscle T reg cells 12 .”
Regulatory T cell dysfunction and immunotherapeutic breakthroughs in type 1 diabetes
Zhou, K.-J., Rong, S.-J., Liu, Y.-C., Sun, F., Wang, T., Yu, Q.-L., & Wang, C.-Y. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1740102 · Cited by 7
“As expected, they suppress in fl ammation at this site, but also produce the growth factor amphiregulin, which enhances the regeneration of muscle satellite cells and promotes muscle repair (74).”
Li, N., Hao, Z., Yang, H., Cai, J., Liu, M., He, J., Gao, R., Shen, Y., Chen, Z., Lu, Y., et al. (2026) · Circulation · doi:10.1161/circulationaha.125.076426 · Cited by 6
Multiple subsets of regulatory T-cells
Kupriyanov, S., Синицкий, А. И., & Dolgushin, I. I. (2020) · Bulletin of Siberian Medicine · doi:10.20538/1682-0363-2020-3-144-155 · Cited by 6
Prencipe, G., Cerveró-Varona, A., Perugini, M., Sulcanese, L., Iannetta, A., Haidar-Montes, A. A., Stöckl, J., Canciello, A., Berardinelli, P., Russo, V., et al. (2024) · iScience · doi:10.1016/j.isci.2024.110508 · Cited by 6
“34,36,37 Starting from these premises, the present study aimed to investigate whether an interaction exists between cyclooxygenase 2 (COX-2)/ PGE 2 /prostaglandin receptor 4 (EP4) and AREG/EGF receptor (EGFR) axes and what role it plays in the paracrine immunosuppressive activities of amniotic…”
Lokwani, R., Fertil, D., Hartigan, D. R., Josyula, A., Ngo, T. B., & Sadtler, K. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202400134 · Cited by 8
Mas‐Bargues, C., Román-Domínguez, A., Sanz‐Ros, J., Romero-García, N., Huete-Acevedo, J., Dromant, M., Cuervo, A. M., Borrás, C., & Viña, J. (2025) · Science Advances · doi:10.1126/sciadv.adr1378 · Cited by 6
“T reg cells are also important players in muscle regeneration as they accumulate in both acute and chronically injured muscle, where they promote satellite cell proliferation and the M1- to-M2 switch in macrophages, thereby changing from a pro-to anti-inflammatory ambient ( 40 ).”
Jiang, X., Luo, T., Zhao, X., Li, P., Gu, X., Wan, C., Xie, X., & Liu, H. (2025) · Immunology · doi:10.1111/imm.13953 · Cited by 6
Innate and adaptive immune mechanisms regulating central nervous system remyelination
Creswell, R., & Dombrowski, Y. (2022) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2021.12.002 · Cited by 6
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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