The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
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.
In the citing paper
“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.
In the citing paper
“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]
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.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Schmitz, J., Owyang, A. M., Oldham, E. R., Song, Y., Murphy, E., McClanahan, T. K., Zurawski, G., Moshrefi, M., Qin, J., Li, X., et al. (2005) · Immunity · doi:10.1016/j.immuni.2005.09.015 · Cited by 3,777 · cited 1×
“…an activation marker; CCR2, important for the recruitment of various leukocyte populations to injured muscle (Warren et al., 2005); and ST2 (encoded by Il1rl1), 1284 Cell 155, 1282–1295, December 5, 2013 ª2013 Elsevier Inc. which is the receptor for the ‘‘alarmin’’ IL-33 (Schmitz et al., 2005).”
Regulatory T cells: mechanisms of differentiation and function
Josefowicz, S. Z., Lu, L.-F., & Rudensky, A. Y. (2012) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141623 · Cited by 2,866 · cited 7×
“A Unique Population of Treg Cells that Accumulates in Skeletal Muscle There is growing appreciation that the Treg compartment is heterogeneous, has multiple functions, and exerts influences exceeding the boundaries of the immune system (Josefowicz et al., 2012).”
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.”
Self-citationArnold, L., Henry, A., Poron, F., Baba-Amer, Y., van Rooijen, N., Plonquet, A., Gherardi, R. K., & Chazaud, B. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070075 · Cited by 2,002 · cited 2×
“As anticipated (Arnold et al., 2007), there was a rapid increase in CD11b+Gr1 myeloid mononuclear cells beginning before day 1, initially a proinflammatory Ly6chi population but switching to an anti-inflammatory Ly6clo population by day 4 (Figure 1A, top).”
Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice
Kim, J. M., Rasmussen, J. P., & Rudensky, A. Y. (2006) · Nature Immunology · doi:10.1038/ni1428 · Cited by 1,827 · cited 4×
“) starting from the time of im Ctx injection and were analyzed 1 week later, a time chosen to avoid the multiorgan autoimmunity provoked by long-term ablation of Treg cells (Kim et al., 2007).”
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
Monticelli (2011) · PubMed · doi:10.1031/ni.2131 · Cited by 1,286
Brochet, X., Lefranc, M., & Giudicelli, V. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn316 · Cited by 1,220 · cited 1×
“Raw sequencing files were filtered for sequence quality, processed in automated fashion, and parsed using IMGT/V-QUEST (Brochet et al., 2008).”
PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells
Cipolletta, D., Feuerer, M., Li, A., Kamei, N., Lee, J., Shoelson, S. E., Benoist, C., & Mathis, D. (2012) · Nature · doi:10.1038/nature11132 · Cited by 1,143 · cited 2×
“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).”
Influential
Cited by
Sorted by citations
Items 401–500 of 1,000
Piñeros, A. R., de Lima, M. H. F., Rodrigues, T. S., Gembre, A. F., Bertolini, T. B., Fonseca, M. M., Berretta, A. A., Ramalho, L. N. Z., Cunha, F. Q., Hori, J. I., et al. (2019) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2019.112496 · Cited by 54
Singh, S. S., Chauhan, S. B., Kumar, A., Kumar, S. B., Engwerda, C. R., Sundar, S., & Kumar, R. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30615 · Cited by 53
Immune and Genome Engineering as the Future of Transplantable Tissue
Elisseeff, J. H., Badylak, S. F., & Boeke, J. D. (2021) · New England Journal of Medicine · doi:10.1056/nejmra1913421 · Cited by 54
Denervation protects limbs from inflammatory arthritis via an impact on the microvasculature
Stangenberg, L., Burzyn, D., Binstadt, B. A., Weissleder, R., Mahmood, U., Benoist, C. O., & Mathis, D. J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1410854111 · Cited by 53
“detailed previously (35) and updated (36).”
Self-citationTranscriptional and Chromatin Dynamics of Muscle Regeneration after Severe Trauma
Aguilar, C. A., Pop, R., Shcherbina, A., Watts, A., Matheny, R. W., Cacchiarelli, D., Han, W. M., Shin, E.-J., Nakhai, S. A., Jang, Y. C., et al. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2016.09.009 · Cited by 53
Self-citationCD49b defines functionally mature Treg cells that survey skin and vascular tissues
Fan, X., Moltedo, B., Mendoza, A., Davydov, A. N., Faire, M. B., Mažutis, L., Sharma, R., Pe’er, D., Chudakov, D. M., & Rudensky, A. Y. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20181442 · Cited by 52
“Furthermore, Treg cells also contribute to repair of NLTs after injury by producing amphiregulin, a ligand of the epidermal growth factor family (Burzyn et al., 2013; Arpaia et al., 2015).”
BackgroundImmunometabolism of pro-repair cells
Singer, B. D., & Chandel, N. S. (2019) · Journal of Clinical Investigation · doi:10.1172/jci124613 · Cited by 53
“In skeletal muscle, Tregs induce repair after both acute and chronic injury in an IL-33–dependent manner (78, 79).”
BackgroundLin, C., Wu, C.-J., Cho, S., Patkar, R., Huth, W. J., Lin, L.-L., Chen, M., Israelsson, E., Betts, J., Niedzielska, M., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01667-y · Cited by 55
Biomaterials‐Based Technologies in Skeletal Muscle Tissue Engineering
Luo, W., Zhang, H., Wan, R., Cai, Y., Liu, Y., Wu, Y., Yang, Y., Chen, J., Zhang, D., Luo, Z., et al. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202304196 · Cited by 53
Stem Cell Transplantation for Muscular Dystrophy: The Challenge of Immune Response
Maffioletti, S. M., Noviello, M., English, K., & Tedesco, F. S. (2014) · BioMed Research International · doi:10.1155/2014/964010 · Cited by 53
Liu, L., Jin, X., Hu, C., Zhang, Y., Zhou, Z., Li, R., & Shen, C. (2018) · Basic Research in Cardiology · doi:10.1007/s00395-018-0669-y · Cited by 52
RetractedNeuronal, stromal, and T-regulatory cell crosstalk in murine skeletal muscle
Wang, K., Yaghi, O., Spallanzani, R. G., Chen, X., Zemmour, D., Lai, N. Y., Chiu, I. M., Benoist, C. O., & Mathis, D. J. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1922559117 · Cited by 52
“Muscle Tregs express high levels of the IL-33 receptor, ST2 (encoded by Il1rl1), and lossand gain-of-function experiments have demonstrated the importance of both muscle Tregs and their expression of ST2 for optimal regeneration after acute injury (7, 13).”
BackgroundSelf-citationInterleukin (IL)‐33: an orchestrator of immunity from host defence to tissue homeostasis
Zhou, Z., Yan, F., & Liu, O. (2020) · Clinical & Translational Immunology · doi:10.1002/cti2.1146 · Cited by 53
“These Tregs reside and accumulate in the muscle after injury increases the differentiation of satellite cells.(71) This was the key observation of the supporting role of IL-33-primed Tregs in the context of muscle injury.”
BackgroundRegulatory T cell heterogeneity and therapy in autoimmune diseases
Zhang, R., Miao, J., & Zhu, P. (2020) · Autoimmunity Reviews · doi:10.1016/j.autrev.2020.102715 · Cited by 52
Improving the Efficacy of Regulatory T Cell Therapy
Baeten, P., Zeebroeck, L. V., Kleinewietfeld, M., Hellings, N., & Broux, B. (2021) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-021-08866-1 · Cited by 52
“Furthermore, Tregs accumulate in acutely injured skeletal muscle in mice and potentiate muscle repair by amphiregulin production [7].”
BackgroundThe inflammatory response of the supraspinatus muscle in rotator cuff tear conditions
Frich, L. H., Rosa-Fernandes, L., Schrøder, H. D., Hejbøl, E. K., Nielsen, P. V., Jørgensen, P. H., Stensballe, A., & Lambertsen, K. L. (2020) · Journal of Shoulder and Elbow Surgery · doi:10.1016/j.jse.2020.08.028 · Cited by 51
Regulatory CAR-T cells in autoimmune diseases: Progress and current challenges
Riët, T., & Chmielewski, M. M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.934343 · Cited by 57
“Furthermore, Treg cells harbor powerful suppressive potential to promote tissue repair (1, 2) and modulate metabolic regulation (3).”
BackgroundGazzerro, E., Baldassari, S., Assereto, S., Fruscione, F., Pistorio, A., Panicucci, C., Volpi, S., Perruzza, L., Fiorillo, C., Minetti, C., et al. (2015) · American Journal Of Pathology · doi:10.1016/j.ajpath.2015.08.010 · Cited by 51
Immune and myodegenerative pathomechanisms in inclusion body myositis
Keller, C. W., Schmidt, J., & Lünemann, J. D. (2017) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.419 · Cited by 57
“Under the control of interleukin (IL)-33, these myophil Tregs execute essential functions in promoting and orchestrating local regeneration upon muscle injury.(117,118) Importantly, they are significantly diminished in aged mice, leading to insufficient muscle repair upon injury.”
BackgroundPatsalos, A., Pap, A., Varga, T., Trencsényi, G., Contreras, G. A., Garai, I., Papp, Z., Dezső, B., Pintye, E., & Nagy, L. (2017) · Journal of Physiology · doi:10.1113/jp274361 · Cited by 50
“Lymphocytes consistently infiltrate the muscle in conditions of chronic injury, including muscular dystrophies (Burzyn et al. 2013; Villalta et al. 2014) and during ageing (Kuswanto et al. 2016).”
BackgroundEllul, P., Mariotti‐Ferrandiz, E., Leboyer, M., & Klatzmann, D. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00167 · Cited by 55
“For instance, in the muscle, Tregs can contribute to muscle repair by the production of amphiregulin (43).”
BackgroundVasanthakumar, A., & Kallies, A. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028506 · Cited by 53
Janakiram, N. B., Valerio, M. S., Goldman, S. M., & Dearth, C. L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413552 · Cited by 51
“Loss of IL-33 in stimulated Tregs resulted in impaired tissue repair [23].”
BackgroundInfluentialXiao, T., Langston, P. K., Muñoz-Rojas, A. R., Jayewickreme, T., Lazar, M. A., Benoist, C. O., & Mathis, D. J. (2022) · Science Immunology · doi:10.1126/sciimmunol.abl7641 · Cited by 54
“(B) Coreclock gene expression by tissue Tregs from published microarray data: VAT (16), skeletal muscle 4 days after cardiotoxin injury (19), and colonic lamina propria (20).”
BackgroundMethodSelf-citationTissue Tregs and Maintenance of Tissue Homeostasis
Shao, Q., Gu, J., Zhou, J., Wang, Q., Li, X., Deng, Z., & Lu, L. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.717903 · Cited by 49
Valero-Pacheco, N., Tang, E. K., Massri, N., Loia, R., Chemerinski, A., Wu, T., Begum, S., El-Naccache, D. W., Gause, W. C., Arora, R., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2123267119 · Cited by 49
Immunological regulation of skeletal muscle adaptation to exercise
Langston, P. K., & Mathis, D. J. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.04.001 · Cited by 55
Self-citationInducing and Administering Tregs to Treat Human Disease
Perdigoto, A. L., Chatenoud, L., Bluestone, J. A., & Herold, K. C. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00654 · Cited by 51
Hurtgen, B. J., Ward, C. L., Wager, C. M. L., Garg, K., Goldman, S. M., Henderson, B. E. P., McKinley, T. O., Greising, S. M., Wenke, J. C., & Corona, B. T. (2017) · Physiological Reports · doi:10.14814/phy2.13362 · Cited by 48
“In addition, regulatory T cells (Tregs) also CD4+, are known to actively suppress proinflammatory responses (Schiaffino et al. 2017), and are linked to regeneration of skeletal muscle by acting on satellite cells (Burzyn et al. 2013; Matta et al. 2014; Arpaia et al. 2015).”
BackgroundHalvorsen, E. C., Franks, S. E., Wadsworth, B. J., Harbourne, B., Cederberg, R. A., Steer, C. A., Martínez-González, I., Calder, J., Lockwood, W. W., & Bennewith, K. L. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1527497 · Cited by 51
Specialized regulatory T cells control venous blood clot resolution through SPARC
Shahneh, F. Z., Grill, A., Klein, M., Frauhammer, F., Bopp, T., Schäfer, K., Raker, V., & Becker, C. (2020) · Blood · doi:10.1182/blood.2020005407 · Cited by 51
PPARγ marks splenic precursors of multiple nonlymphoid-tissue Treg compartments
Li, C., Muñoz-Rojas, A. R., Wang, G., Mann, A. O., Benoist, C. O., & Mathis, D. J. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2025197118 · Cited by 55
Self-citationRecent update on craniofacial tissue engineering
Emara, A., & Shah, R. (2021) · Journal of Tissue Engineering · doi:10.1177/20417314211003735 · Cited by 49
Innate Control of Tissue-Reparative Human Regulatory T Cells
Lam, A. J., MacDonald, K. N., Pesenacker, A. M., Juvet, S. C., Morishita, K. A., Bressler, B., iGenoMed Consortium, Pan, J. G., Sidhu, S. S., Rioux, J. D., et al. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1801330 · Cited by 47
“Accordingly, AREG mRNA and protein expression is highly enriched in mouse Tregs compared with Tconvs, particularly in Tregs resident in nonlymphoid tissues (5, 9, 11, 12, 42).”
BackgroundInfluentialGlaubitz, J., Wilden, A., Golchert, J., Homuth, G., Völker, U., Bröker, B. M., Thiele, T., Lerch, M. M., Mayerle, J. V., Aghdassi, A. A., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32195-2 · Cited by 52
Whytock, K. L., & Goodpaster, B. H. (2025) · Circulation Research · doi:10.1161/circresaha.125.325532 · Cited by 57
Antigen-specific Treg cells in immunological tolerance: implications for allergic diseases
Abdel-Gadir, A., Massoud, A. H., & Chatila, T. A. (2018) · F1000Research · doi:10.12688/f1000research.12650.1 · Cited by 48
Regulatory T cells: Master thieves of the immune system
Akkaya, B., & Shevach, E. M. (2020) · Cellular Immunology · doi:10.1016/j.cellimm.2020.104160 · Cited by 52
Bergmann, C. B., Beckmann, N., Salyer, C. E., Crisologo, P. A., Nomellini, V., & Caldwell, C. C. (2020) · Shock · doi:10.1097/shk.0000000000001675 · Cited by 50
Dual Immune Regulatory Roles of Interleukin-33 in Pathological Conditions
Guo, H., Bossila, E. A., Ma, X., Zhao, C., & Zhao, Y. X. (2022) · Cells · doi:10.3390/cells11203237 · Cited by 54
Healing the Broken Heart; The Immunomodulatory Effects of Stem Cell Therapy
Wagner, M. J., Khan, M., & Mohsin, S. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00639 · Cited by 48
“Skeletal muscle Tregs contain a distinct T-cell receptor repertoire (TCR) that is only expressed on Tregs that influx into the injured skeletal muscle, not on systemic, peripheral Tregs occupying the systemic lymph nodes or spleen (140).”
BackgroundInfluentialSignaling and functions of interleukin-33 in immune regulation and diseases
Yi, X.-M., Lian, H., & Li, S. (2022) · Cell Insight · doi:10.1016/j.cellin.2022.100042 · Cited by 46
Regulatory T cells in autoimmune kidney diseases and transplantation
Mikami, N., & Sakaguchi, S. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-023-00733-w · Cited by 46
Regulatory T cells in dominant immunologic tolerance
Georgiev, P., Benamar, M., Han, S., Haigis, M. C., Sharpe, A. H., & Chatila, T. A. (2023) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2023.09.025 · Cited by 51
de la Fuente, A. G., Dittmer, M., Heesbeen, E. J., Gallardo, N. D. L. V., White, J. A., Young, A., McColgan, T., Dashwood, A., Mayne, K., Cabeza‐Fernández, S., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45742-w · Cited by 46
Corona, B. T., Henderson, B. E. P., Ward, C. L., & Greising, S. M. (2017) · Physiological Reports · doi:10.14814/phy2.13249 · Cited by 47
“Also, regulatory T cells (Tregs) may actively suppress exacerbated pro-inflammatory responses (Schiaffino et al. 2017), and may also promote regeneration of skeletal muscle by acting on satellite cells (Burzyn et al. 2013; Matta et al. 2014; Arpaia et al. 2015).”
BackgroundA nonimmune function of T cells in promoting lung tumor progression
Green, J. A., Arpaia, N., Schizas, M., Dobrin, A., & Rudensky, A. Y. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20170356 · Cited by 45
“Although much attention has been directed toward studying how conventional T cells respond to tumor antigens to limit tumor growth, and how restoring and boosting T cell responsiveness can result in effective cancer therapy, recent findings that T cells can also participate in tissue repair suggest that they may affec…”
BackgroundForcina, L., Miano, C., & Musarò, A. (2018) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2018.05.001 · Cited by 46
Schjenken, J. E., Moldenhauer, L. M., Zhang, B., Care, A. S., Groome, H. M., Chan, H. Y., Hope, C. M., Barry, S. C., & Robertson, S. A. (2020) · Mucosal Immunology · doi:10.1038/s41385-020-0255-0 · Cited by 46
Skeletal muscle as an experimental model of choice to study tissue aging and rejuvenation
Etienne, J., Liu, C., Skinner, C. M., Conboy, M. J., & Conboy, I. M. (2020) · Skeletal Muscle · doi:10.1186/s13395-020-0222-1 · Cited by 53
A Stromal Progenitor and ILC2 Niche Promotes Eosinophilia in Skeletal Muscle
Kastenschmidt, J. M., Coulis, G., Farahat, P. K., Pham, P., Rios, R., Cristal, T. T., Mannaa, A. H., Ayer, R. E., Yahia, R., Deshpande, A. A., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2021.108997 · Cited by 47
“IL-33 and IL-2c promote regeneration during acute muscle injuries through their action on muscle Tregs (Burzyn et al., 2013; Kuswanto et al., 2016).”
BackgroundInfluentialYu, S., Chen, X., Liu, Y., Zhuang, X. Y., Wang, A. C., Liu, X. M., & Zhu, S. Y. (2022) · International Endodontic Journal · doi:10.1111/iej.13721 · Cited by 46
IL-17A–producing γδT cells promote muscle regeneration in a microbiota-dependent manner
Mann, A. O., Hanna, B. S., Muñoz-Rojas, A. R., Sandrock, I., Prinz, I., Benoist, C. O., & Mathis, D. J. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20211504 · Cited by 49
Self-citationNature vs. nurture: FOXP3, genetics, and tissue environment shape Treg function
Raugh, A., Allard, D., & Bettini, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.911151 · Cited by 46
Wang, G., Muñoz-Rojas, A. R., Spallanzani, R. G., Franklin, R. A., Benoist, C. O., & Mathis, D. J. (2024) · Immunity · doi:10.1016/j.immuni.2024.04.002 · Cited by 47
Self-citationLevels of S100B protein drive the reparative process in acute muscle injury and muscular dystrophy
Riuzzi, F., Beccafico, S., Sagheddu, R., Chiappalupi, S., Giambanco, I., Bereshchenko, O., Riccardi, C., Sorci, G., & Donato, R. (2017) · Scientific Reports · doi:10.1038/s41598-017-12880-9 · Cited by 45
Human Tregs at the materno-fetal interface show site-specific adaptation reminiscent of tumor Tregs
Wienke, J., Brouwers, L., van der Burg, L. M., Mokrý, M., Scholman, R. C., Nikkels, P. G. J., van Rijn, B. B., & van Wijk, F. (2020) · JCI Insight · doi:10.1172/jci.insight.137926 · Cited by 43
“Also, others have reported that nonlymphoid tissue Tregs display an activated phenotype compared with lymphoid organ and circulating Tregs (12, 20, 73).”
InfluentialTumor resident regulatory T cells
Glasner, A., & Plitas, G. (2021) · Seminars in Immunology · doi:10.1016/j.smim.2021.101476 · Cited by 47
Phenotypic and Functional Diversity in Regulatory T Cells
Sjaastad, L. E., Owen, D. L., Tracy, S. I., & Farrar, M. A. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.715901 · Cited by 50
Development and Function of Effector Regulatory T Cells
Teh, P. P., Vasanthakumar, A., & Kallies, A. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2015.08.005 · Cited by 42
An Update on Lymphocyte Subtypes in Asthma and Airway Disease
Moldaver, D. M., Larché, M., & Rudulier, C. D. (2016) · CHEST Journal · doi:10.1016/j.chest.2016.10.038 · Cited by 44
Zhang, R., Xu, K., Shao, Y., Sun, Y., Saredy, J., Cutler, E., Tian, Y., Liu, M., Liu, L., Drummer, C., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.632239 · Cited by 43
Ozone Pollution, Oxidative Stress, Regulatory T Cells and Antioxidants
Rivas-Arancibia, S., Hernández-Orozco, E., Rodrı́guez-Martı́nez, E., Valdés‐Fuentes, M., Cornejo-Trejo, V., Pérez-Pacheco, N., Dorado-Martı́nez, C., Zequeida-Carmona, D., & Caleti, I. E. (2022) · Antioxidants · doi:10.3390/antiox11081553 · Cited by 45
“Treg cells are present in healthy tissues and, after tissue injury, promote tissue regeneration in a manner dependent on the transmembrane glycoprotein of the epidermoid growth factor family or protein amphiregulin or AREG [20].”
BackgroundTreg-Centric View of Immunosuppressive Drugs in Transplantation: A Balancing Act
Camirand, G., & Riella, L. V. (2016) · American Journal of Transplantation · doi:10.1111/ajt.14029 · Cited by 43
Harnessing Advances in T Regulatory Cell Biology for Cellular Therapy in Transplantation
Lam, A. J., Hoeppli, R. E., & Levings, M. K. (2017) · Transplantation · doi:10.1097/tp.0000000000001757 · Cited by 41
“AREG acts directly onmuscle satellite cells in vitro and its administration to injured mice improves muscle repair.(79) In this section, we will discuss the tissue repair capacity of Treg cells and their possible applications for transplantation.”
BackgroundInfluentialDehydrated Human Amnion Chorion Membrane as Treatment for Pediatric Burns
Ahuja, N., Jin, R. M., Powers, C., Billi, A., & Bass, K. D. (2019) · Advances in Wound Care · doi:10.1089/wound.2019.0983 · Cited by 45
An emerging role of regulatory T-cells in cardiovascular repair and regeneration
Fung, T. H. W., Yang, Y., & Lui, K. O. (2020) · Theranostics · doi:10.7150/thno.47118 · Cited by 44
Redressing the interactions between stem cells and immune system in tissue regeneration
Fang, J., Feng, C., Chen, W., Hou, P., Liu, Z., Zuo, M., Han, Y., Xu, C., Melino, G., Verkhratsky, A., et al. (2021) · Biology Direct · doi:10.1186/s13062-021-00306-6 · Cited by 44
The Yin and Yang of Targeting KLRG1+ Tregs and Effector Cells
Borys, S. M., Bag, A. K., Brossay, L., & Adeegbe, D. O. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.894508 · Cited by 44
Tuft cells and fibroblasts promote thymus regeneration through ILC2-mediated type 2 immune response
Nevo, S., Frenkel, N., Kadouri, N., Gome, T., Rosenthal, N., Givony, T., Avin, A., Cruz, C. P., Kedmi, M., Lindzen, M., et al. (2024) · Science Immunology · doi:10.1126/sciimmunol.abq6930 · Cited by 42
Regulatory T Cells in Kidney Transplantation: New Directions?
Braza, F., Durand, M., Degauque, N., & Brouard, S. (2015) · American Journal of Transplantation · doi:10.1111/ajt.13395 · Cited by 44
“One very interesting example is the recent description of an amphiregulin-secreting Treg subset involved in muscle repair and regeneration (124).”
BackgroundTherapeutic Potential of Immunoproteasome Inhibition in Duchenne Muscular Dystrophy
Farini, A., Sitzia, C., Cassani, B., Cassinelli, L., Rigoni, R., Colleoni, F., Fusco, N., Gatti, S., Bella, P., Villa, C., et al. (2016) · Molecular Therapy · doi:10.1038/mt.2016.162 · Cited by 44
T-regulatory cells exhibit a biphasic response to prolonged endurance exercise in humans
Clifford, T., Wood, M. J., Stocks, P., Howatson, G., Stevenson, E., & Hilkens, C. (2017) · European Journal of Applied Physiology · doi:10.1007/s00421-017-3667-0 · Cited by 38
“Burzyn et al. (2013) found that Tregs accumulate in damaged skeletal muscle of mice, lending some support to this idea.”
Phenotypic and Functional Properties of Tumor-Infiltrating Regulatory T Cells
Lee, G. R. (2017) · Mediators of Inflammation · doi:10.1155/2017/5458178 · Cited by 44
“In addition, Treg cells acquire distinct immunomodulatory mechanisms when residing in different peripheral tissues [58].”
BackgroundRole of the IL-33/ST2L axis in colorectal cancer progression
Akimoto, M., & Takenaga, K. (2018) · Cellular Immunology · doi:10.1016/j.cellimm.2017.12.014 · Cited by 42
Regulatory T cells are required for normal and activin‐promoted wound repair in mice
Haertel, E., Joshi, N., Hiebert, P., Köpf, M., & Werner, S. (2018) · European Journal of Immunology · doi:10.1002/eji.201747395 · Cited by 42
Regenerating CNS myelin: Emerging roles of regulatory T cells and CCN proteins
Gallardo, N. D. L. V., Dittmer, M., Dombrowski, Y., & Fitzgerald, D. C. (2018) · Neurochemistry International · doi:10.1016/j.neuint.2018.11.024 · Cited by 42
“Furthermore, Treg-derived amphiregulin (AR) was critical in this setting (Burzyn et al., 2013).”
BackgroundTorre-Villalvazo, I., Alemán, G., Valle‐Rios, R., & Noriega, L. G. (2019) · Nutrition Research · doi:10.1016/j.nutres.2019.06.006 · Cited by 45
Stability and Maintenance of Foxp3+ Treg Cells in Non-lymphoid Microenvironments
Korn, T., & Muschaweckh, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02634 · Cited by 43
Gene therapy with regulatory T cells: A beneficial alliance
Biswas, M., Kumar, S. R. P., Terhorst, C., & Herzog, R. W. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00554 · Cited by 41
Papait, A., Cancedda, R., Mastrogiacomo, M., & Poggi, A. D. (2016) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.2361 · Cited by 41
High self-reactivity drives T-bet and potentiates Treg function in tissue-specific autoimmunity
Sprouse, M. L., Scavuzzo, M. A., Blum, S. I., Shevchenko, I., Lee, T., Makedonas, G., Borowiak, M., Bettini, M. L., & Bettini, M. (2018) · JCI Insight · doi:10.1172/jci.insight.97322 · Cited by 40
New Insights Into the Biology of CD8 Regulatory T Cells
Nakagawa, H., Wang, L., Cantor, H., & Kim, H. (2018) · Advances in immunology · doi:10.1016/bs.ai.2018.09.001 · Cited by 41
Moldenhauer, L. M., Schjenken, J. E., Hope, C. M., Green, E. S., Zhang, B., Eldi, P., Hayball, J. D., Barry, S. C., & Robertson, S. A. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1900084 · Cited by 41
“consequences for the kinetics of muscle repair and growth (68).”
BackgroundMethodImmunometabolism of regulatory T cells in cancer
Saravia, J., & Chi, H. (2025) · Oncogene · doi:10.1038/s41388-025-03458-1 · Cited by 45
“However, it is now understood that T reg cell functions extend to homeostatic tissue maintenance (e.g., in the skin [169]) and wound repair (e.g., in damaged muscle tissue [170]), and adoptive T reg cell therapies have been proposed for treatment of non-immune diseases [171].”
Amphiregulin may be a new biomarker of classically activated macrophages
Chen, M., Liu, G., Mu, H., Zhou, M., Zhang, S., & Xu, Y. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.09.037 · Cited by 38
Tertiary lymphoid organs in systemic autoimmune diseases: pathogenic or protective?
Shipman, W. D., Dasoveanu, D., & Lu, T. T. (2017) · F1000Research · doi:10.12688/f1000research.10595.1 · Cited by 42
The Janus Face of IL-33 Signaling in Tumor Development and Immune Escape
Choi, M.-R., Sosman, J. A., & Zhang, B. (2021) · Cancers · doi:10.3390/cancers13133281 · Cited by 40
“IL-33 stimulates ST2Treg cells and AREG expression, which enhances immune regulatory functions and tissue repair [104,105].”
BackgroundRegulatory T cell-derived IL-1Ra suppresses the innate response to respiratory viral infection
Griffith, J. W., Faustino, L., Cottrell, V. I., Nepal, K., Hariri, L. P., Chiu, R. S.-Y., Jones, M. C., Julé, A. M., Gabay, C., & Luster, A. D. (2023) · Nature Immunology · doi:10.1038/s41590-023-01655-2 · Cited by 45
“…and profiles based on their tissue of residence, they are typically derived from the thymus and express the IL-33 receptor ST2 and the type 2 helper T cell-associated transcription factor GATA3, suggesting that these homeostatic tissue T reg cells share a common differentiation pathway 9,10 .”
BackgroundMyocardial fibrosis seen through the lenses of T-cell biology
Ramos, G. C., Hofmann, U., & Frantz, S. (2016) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2016.01.018 · Cited by 41
Okerblom, J., Schwarz, F., Olson, J., Fletes, W., Ali, S. R., Martin, P. T., Glass, C. K., Nizet, V., & Varki, A. P. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601471 · Cited by 39
Jin, R. M., Warunek, J., & Wohlfert, E. A. (2018) · ImmunoHorizons · doi:10.4049/immunohorizons.1800024 · Cited by 40
Mock, J. R., Dial, C. F., Tune, M. K., Norton, D. L., Martin, J. R., Gomez, J. C., Hagan, R. S., Dang, H., & Doerschuk, C. M. (2019) · JCI Insight · doi:10.1172/jci.insight.124958 · Cited by 41
“Our prior studies demonstrate that Tregs enhance alveolar epithelial proliferation after injury in vivo and that Tregs directly promote AT2 proliferation in vitro, in part by a contact-independent mechanism, through the expression of keratinocyte growth factor (KGF) (16).”
BackgroundInfluentialFang, J., Zhang, S., Liu, Z., Pan, Y., Cao, L., Hou, P., Chen, Y., Zhang, Y., Li, X., Liu, R., et al. (2020) · Stem Cells Translational Medicine · doi:10.1002/sctm.19-0447 · Cited by 41
Chen, C., & Poss, K. D. (2017) · Annual Review of Genetics · doi:10.1146/annurev-genet-120116-024554 · Cited by 44
“Injury causes clotting and inflammation, and there are many recent studies that report evidence for pro-regenerative roles of immune cells like macrophages and T-cells (12; 67; 87; 135).”
BackgroundHaunhorst, S., Bloch, W., Javelle, F., Krüger, K., Baumgart, S., Drube, S., Lemhöfer, C., Reuken, P. A., Stallmach, A., Müller, M. K., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1070994 · Cited by 43
The Generation and Regulation of Tissue‐Resident Tregs and Their Role in Autoimmune Diseases
Wang, S., Zou, X., Zhang, Y., Wang, X., Yang, W., & Li, Y. (2020) · Journal of Immunology Research · doi:10.1155/2020/8815280 · Cited by 38
“Areg belongs to the family of epithelial growth factors, a growth factor overexpressed by muscle Tregs that can enhance muscle regeneration [51].”
Current status and perspectives of regulatory T cell-based therapy
Qu, G., Chen, J., Li, Y., Yuan, Y., Liang, R., & Li, B. (2022) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2022.05.005 · Cited by 40
Dubuisson, N., Versele, R., Planchon, C., Selvais, C. M., Noël, L., Abou‐Samra, M., & de Carrizosa, M. A. D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232416080 · Cited by 41
“In DMD, degenerating dystrophin-absent fibres secrete proinflammatory cytokines and chemokines, implying the continuous recruitment of the above-mentioned immune cells which in turn activate M1 macrophages, leading to a chronic inflammatory state producing high concentrations of proinflammatory cytokines such as IFNγ,…”
BackgroundClancy‐Thompson, E., Chen, G. Z., Tyler, P. M., Servos, M. M., Barisa, M., Brennan, P. J., Ploegh, H. L., & Dougan, S. K. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700214 · Cited by 40
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
