The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Regulatory T cells promote myelin regeneration in the central nervous system
Open accessAbstract
Regeneration of myelin is a dynamic, yet enigmatic process. Dombrowski et al. uncover a central role for regulatory T (Treg) cells in driving oligodendrocyte differentiation, in part via CCN3, a novel factor in Treg function and oligodendrocyte biology. This identifies Treg cells as key cellular players in efficient remyelination. Regeneration of CNS myelin involves differentiation of oligodendrocytes from oligodendrocyte progenitor cells. In multiple sclerosis, remyelination can fail despite abundant oligodendrocyte progenitor cells, suggesting impairment of oligodendrocyte differentiation. T cells infiltrate the CNS in multiple sclerosis, yet little is known about T cell functions in remyelination. We report that regulatory T cells (Treg) promote oligodendrocyte differentiation and (re)myelination. Treg-deficient mice exhibited substantially impaired remyelination and oligodendrocyte differentiation, which was rescued by adoptive transfer of Treg. In brain slice cultures, Treg accelerated developmental myelination and remyelination, even in the absence of overt inflammation. Treg directly promoted oligodendrocyte progenitor cell differentiation and myelination in vitro. We identified CCN3 as a Treg-derived mediator of oligodendrocyte differentiation and myelination in vitro. These findings reveal a new regenerative function of Treg in the CNS, distinct from immunomodulation. Although the cells were originally named 'Treg' to reflect immunoregulatory roles, this also captures emerging, regenerative Treg functions.
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
“In a recent study, Dombrowski and colleagues demonstrated that T reg cells promote oligodendrocyte differentiation and myelin repair counteracting the well-known pro-inflammatory and cytotoxic effects of T h 1, T h 17, and cytotoxic T cell subpopulations (Dombrowski et al., 2017).”
From Cuprizone‐induced demyelination triggers a CD8‐pronounced T cell recruitment (2021) · cites this paper as Dombrowski et al., 2017
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 principle, both detrimental and reparative effects of CD3 + lymphocytes have been demonstrated in MS animal models including the delay of, and promotion of remyelination (Baxi et al., 2015;Bieber, Kerr, & Rodriguez, 2003;Dombrowski et al., 2017;Wagner, Roqué, Mileur, Liggitt, & Goverman, 2020;Wang et al., 2010).”
From Cuprizone‐induced demyelination triggers a CD8‐pronounced T cell recruitment (2021) · cites this paper as Dombrowski et al., 2017
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“For example, Treg cells can promote oligodendrocyte progenitor cell differentiation and, thereby, myelin regeneration in the central nervous system [450].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [450]
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
NIH Image to ImageJ: 25 years of image analysis
Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012) · Nature Methods · doi:10.1038/nmeth.2089 · Cited by 64,638
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610
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
M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination
Miron, V. E., Boyd, A., Zhao, J.-W., Yuen, T. J., Ruckh, J. M., Shadrach, J. L., van Wijngaarden, P., Wagers, A. J., Williams, A., Franklin, R. J. M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3469 · Cited by 1,777 · cited 2×
“Remyelination frequently occurs in the context of innate and adaptive immune responses3,4.”
Self-citationOligodendroglia metabolically support axons and contribute to neurodegeneration
Lee, Y., Morrison, B. M., Li, Y., Lengacher, S., Farah, M. H., Hoffman, P. N., Liu, Y., Tsingalia, A., Jin, L., Zhang, P.-W., et al. (2012) · Nature · doi:10.1038/nature11314 · Cited by 1,664
Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity
Fünfschilling, U., Supplie, L. M., Mahad, D., Boretius, S., Saab, A. S., Edgar, J., Brinkmann, B. G., Kassmann, C. M., Tzvetanova, I. D., Möbius, W., et al. (2012) · Nature · doi:10.1038/nature11007 · Cited by 1,523
A Special Population of Regulatory T Cells Potentiates Muscle Repair
Burzyn, D., Kuswanto, W., Kolodin, D., Shadrach, J. L., Cerletti, M., Jang, Y., Sefik, E., Tan, T. G., Wagers, A. J., Benoist, C., et al. (2013) · Cell · doi:10.1016/j.cell.2013.10.054 · Cited by 1,234
A Distinct Function of Regulatory T Cells in Tissue Protection
Arpaia, N., Green, J. A., Moltedo, B., Arvey, A., Hemmers, S., Yuan, S., Treuting, P. M., & Rudensky, A. Y. (2015) · Cell · doi:10.1016/j.cell.2015.08.021 · Cited by 991
Weirather, J., Hofmann, U., Beyersdorf, N., Ramos, G. C., Vogel, B., Frey, A., Ertl, G., Kerkau, T., & Frantz, S. (2014) · Circulation Research · doi:10.1161/circresaha.115.303895 · Cited by 727
Impaired adult myelination in the prefrontal cortex of socially isolated mice
Liu, J., Dietz, K., DeLoyht, J. M., Pedre, X., Kelkar, D., Kaur, J., Vialou, V., Lobo, M. K., Dietz, D. M., Nestler, E. J., et al. (2012) · Nature Neuroscience · doi:10.1038/nn.3263 · Cited by 685
All in the CCN family: essential matricellular signaling modulators emerge from the bunker
Leask, A., & Abraham, D. (2006) · Journal of Cell Science · doi:10.1242/jcs.03270 · Cited by 666
Rejuvenation of Regeneration in the Aging Central Nervous System
Ruckh, J. M., Zhao, J.-W., Shadrach, J. L., van Wijngaarden, P., Rao, T. N., Wagers, A. J., & Franklin, R. J. M. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2011.11.019 · Cited by 649
Self-citationMicropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis
Mei, F., Fancy, S. P. J., Shen, Y. A., Niu, J., Zhao, C., Presley, B., Miao, E., Lee, S., Mayoral, S. R., Redmond, S., et al. (2014) · Nature Medicine · doi:10.1038/nm.3618 · Cited by 595
Self-citationRetinoid X receptor gamma signaling accelerates CNS remyelination
Huang, J. K., Jarjour, A. A., Nait Oumesmar, B., Kerninon, C., Williams, A., Krezel, W., Kagechika, H., Bauer, J., Zhao, C., Evercooren, A. B.-V., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2702 · Cited by 547
Self-citationbHLH Transcription Factor Olig1 Is Required to Repair Demyelinated Lesions in the CNS
Arnett, H. A., Fancy, S. P. J., Alberta, J. A., Zhao, C., Plant, S. R., Kaing, S., Raine, C. S., Rowitch, D. H., Franklin, R. J. M., & Stiles, C. D. (2004) · Science · doi:10.1126/science.1103709 · Cited by 416
Self-citationKotter, M. R., Setzu, A., Sim, F. J., Van Rooijen, N., & Franklin, R. J. M. (2001) · Glia · doi:10.1002/glia.1085 · Cited by 385
Self-citationNOV (nephroblastoma overexpressed) and the CCN family of genes: structural and functional issues
Perbal, B. (2001) · Molecular Pathology · doi:10.1136/mp.54.2.57 · Cited by 345
Self-citationWoodruff, R. H., Fruttiger, M., Richardson, W. D., & Franklin, R. J. M. (2004) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2003.10.014 · Cited by 335
Self-citationHall, S. M. (1972) · Journal of Cell Science · doi:10.1242/jcs.10.2.535 · Cited by 271
Saxena, A., Dobaczewski, M. P., Rai, V., Haque, Z. K., Chen, W., Li, N., & Frangogiannis, N. G. (2014) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00328.2014 · Cited by 220
CCN3 (NOV) Is a Novel Angiogenic Regulator of the CCN Protein Family
Lin, C. G., Leu, S.-J. J., Chen, N., Tebeau, C. M., Lin, S.-X., Yeung, C. Y., & Lau, L. F. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302028200 · Cited by 218
Ousman, S. S., & David, S. (2000) · Glia · doi:10.1002/(sici)1098-1136(200003)30:1 · Cited by 209
Lysolecithin induces demyelination in vitro in a cerebellar slice culture system
Birgbauer, E., Rao, T. S., & Webb, M. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20248 · Cited by 202
Efficient central nervous system remyelination requires T cells
Bieber, A. J., Kerr, S., & Rodriguez, M. (2003) · Annals of Neurology · doi:10.1002/ana.10578 · Cited by 196
Wang, Y., Kissenpfennig, A., Mingueneau, M., Richelme, S., Perrin, P., Chevrier, S., Genton, C., Lucas, B., Santo, J. P. D., Acha‐Orbea, H., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.3.1565 · Cited by 188
Self-citationCNS Repair Requires Both Effector and Regulatory T Cells with Distinct Temporal and Spatial Profiles
Rapôso, C., Graubardt, N., Cohen, M., Eitan, C., London, A., Berkutzki, T., & Schwartz, M. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0076-14.2014 · Cited by 162
novH: differential expression in developing kidney and Wilm's tumors.
Chevalier, G., Yeger, H., Martinerie, C., Laurent, M., Alami, J., Schofield, P. N., & Perbal, B. (1998) · Europe PMC (PubMed Central) · Cited by 142
Self-citationZhao, C., Li, W.-W., & Franklin, R. J. M. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.06.008 · Cited by 142
Self-citationCentral nervous system remyelination in culture — A tool for multiple sclerosis research
Zhang, H., Jarjour, A. A., Boyd, A. L., & Williams, A. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.04.009 · Cited by 140
Self-citationCCN proteins: A centralized communication network
Perbal, B. (2013) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-013-0193-7 · Cited by 90
Self-citationPINK1 Deficiency Enhances Inflammatory Cytokine Release from Acutely Prepared Brain Slices
Kim, J., Byun, J.-W., Choi, I., Kim, B., Jeong, H., Jou, I., & Joe, E.-H. (2013) · Experimental Neurobiology · doi:10.5607/en.2013.22.1.38 · Cited by 71
By, S., Cai, W.-Q., Zhang, C.-G., Martinez, V., Lombet, A., & Perbal, B. (2001) · Molecular Pathology · doi:10.1136/mp.54.3.184 · Cited by 69
Self-citationSheridan, G. K., & Dev, K. K. (2011) · Glia · doi:10.1002/glia.22272 · Cited by 60
Differential expression of novH and CTGF in human glioma cell lines
Xin, L. W., Martinerie, C., Zumkeller, W., Westphal, M., & Perbal, B. (1996) · Molecular Pathology · doi:10.1136/mp.49.2.m91 · Cited by 52
Self-citationLimitations of Foxp3+ Treg depletion following viral infection in DEREG mice
Christiaansen, A. F., Boggiatto, P. M., & Varga, S. M. (2014) · Journal of Immunological Methods · doi:10.1016/j.jim.2014.03.005 · Cited by 49
Promotion of dentin regeneration via CCN3 modulation on Notch and BMP signaling pathways
Wang, X., He, H., Wu, X., Hu, J., & Tan, Y. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2013.12.029 · Cited by 41
Advantages of Foxp3+regulatory T cell depletion using DEREG mice
Mayer, C. T., Lahl, K., Milanez‐Almeida, P., Watts, D., Dittmer, U., Fyhrquist, N., Huehn, J., Köpf, M., Kretschmer, K., Rouse, B. T., et al. (2014) · Immunity Inflammation and Disease · doi:10.1002/iid3.33 · Cited by 39
NOV/CCN3 promotes maturation of cerebellar granule neuron precursors
Dréau, G. L., Nicot, A. B., Bénard, M., Thibout, H., Vaudry, D., Martinerie, C., & Laurent, M. (2009) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2009.02.011 · Cited by 29
zu Hörste, G. M., Zozulya, A. L., El-Haddad, H., Lehmann, H. C., Hartung, H., Wiendl, H., & Kieseier, B. C. (2010) · Journal of Immunological Methods · doi:10.1016/j.jim.2010.01.012 · Cited by 22
Ling, C., Verbny, Y., Banks, M. I., Sándor, M., & Fábry, Z. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.12.8393 · Cited by 17
[Myelin formation in central nervous system tissue cultures].
Hild, W. (2000) · PubMed · Cited by 8
Flagged first, then by citations
Research works printed but not linked: 1
- Hild, W. Myelinbildung in Kulturen des Zentralnervensystems. Verh. Anat. Ges. 53, 315–317 (1956-1957).
Cited by
Sorted by citations
The blood–brain barrier and blood–tumour barrier in brain tumours and metastases
Arvanitis, C., Ferraro, G. B., & Jain, R. K. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0205-x · Cited by 1,919
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
Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
Cossarizza, A., Chang, H., Radbruch, A., Acs, A., Adam, D., Adam‐Klages, S., Agace, W. W., Aghaeepour, N., Akdiş, M., Allez, M., et al. (2019) · European Journal of Immunology · doi:10.1002/eji.201970107 · Cited by 1,007
Regenerating CNS myelin — from mechanisms to experimental medicines
Franklin, R. J. M., & ffrench-Constant, C. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.136 · Cited by 647
Self-citationOligodendrocytes in development, myelin generation and beyond
Kuhn, S., Gritti, L., Crooks, D., & Dombrowski, Y. (2019) · Cells · doi:10.3390/cells8111424 · Cited by 625
Self-citation
Metadata
- Authors
- Dombrowski, Y., O'Hagan, T., Dittmer, M., Penalva, R., Mayoral, S. R., Bankhead, P., Fleville, S., Eleftheriadis, G., Zhao, C., Naughton, M., Hassan, R., Moffat, J., Falconer, J., Boyd, A., Hamilton, P., Allen, I. V., Kissenpfennig, A., Moynagh, P. N., Evergren, E., Perbal, B., Williams, A. C., Ingram, R. J., Chan, J. R., Franklin, R. J. M., & Fitzgerald, D. C.
- Affiliations
- Queen's University Belfast (GB)
- University of California, San Francisco (US)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- MRC Centre for Regenerative Medicine (GB)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Fitzgerald, Denise C
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2017-03-13
- Volume
- 20
- Issue
- 5
- Pages
- 674-680
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC5409501
- OpenAlex
- W2595073340
- Cited by
- 533
- References
- 41
- Citations by year
- 2026: 47 · 2025: 60 · 2024: 77 · 2023: 62 · 2022: 60 · 2021: 61 · 2020: 55 · 2019: 57 · 2018: 37 · 2017: 16
- FWCI
- 19.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Maynooth University ePrints and eTheses Archive (Maynooth University) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion, other-oa)
- eScholarship (California Digital Library) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Memorial Sloan-Kettering Cancer Center
- Wellcome Trust (WT104915MA, 110138/Z/15/Z, 110138, /Z/15/Z, 097922/Z/11/Z)
- Leverhulme Trust (ECF-2014-390)
- Multiple Sclerosis Society
- Rosetrees Trust
- National Institutes of Health
- Directorate for Biological Sciences
- Medical Research Council (MC_PC_12009, MR/K017047/1, WT104915MA)
- Biotechnology and Biological Sciences Research Council (BB/J01026X/1, BB/N003721/1)
- National Institute of General Medical Sciences (K12GM081266)
- National Institute of Neurological Disorders and Stroke (R01NS095889)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Keywords
- regulatory T cells, remyelination, oligodendrocyte differentiation, oligodendrocyte precursor cells, CCN3, multiple sclerosis, myelination, central nervous system regeneration
- MeSH terms
- Animals, Brain, Cell Differentiation, Female, Male, Myelin Sheath, Oligodendroglia, Regeneration, Stem Cells, T-Lymphocytes, Regulatory, Mice, Nephroblastoma Overexpressed Protein
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
