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.
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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]
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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“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]
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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“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
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 3,773 · 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).”
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Control of adaptive immunity by the innate immune system
Iwasaki, A., & Medzhitov, R. (2015) · Nature Immunology · doi:10.1038/ni.3123 · Cited by 2,160
Pathophysiology of Inflammatory Bowel Diseases
Chang, J. T. (2020) · New England Journal of Medicine · doi:10.1056/nejmra2002697 · Cited by 1,295
The far-reaching scope of neuroinflammation after traumatic brain injury
Simon, D. W., McGeachy, M. J., Bayır, H., Clark, R. S. B., Loane, D. J., & Kochanek, P. M. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.13 · Cited by 1,190
Interleukin-33 in health and disease
Liew, F. Y., Girard, J., & Turnquist, H. R. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.95 · Cited by 1,178
Regulatory T Cells and Human Disease
Sakaguchi, S., Mikami, N., Wing, J. B., Tanaka, A., Ichiyama, K., & Ohkura, N. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041717 · Cited by 1,163
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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