Regulatory T cells expressing interleukin 10 develop from Foxp3+ and Foxp3− precursor cells in the absence of interleukin 10
Abstract
CD4(+) regulatory T cells (T(reg) cells) that produce interleukin 10 (IL-10) are important contributors to immune homeostasis. We generated mice with a 'dual-reporter' system of the genes encoding IL-10 and the transcription factor Foxp3 to track T(reg) subsets based on coordinate or differential expression of these genes. Secondary lymphoid tissues, lung and liver had enrichment of Foxp3(+)IL-10(-) T(reg) cells, whereas the large and small intestine had enrichment of Foxp3(+)IL-10(+) and Foxp3(-)IL-10(+) T(reg) cells, respectively. Although negative for Il10 expression, both Foxp3(+) and Foxp3(-) CD4(+) thymic precursor cells gave rise to peripheral IL-10(+) T(reg) cells, with only Foxp3(-) precursor cells giving rise to all T(reg) subsets. Each T(reg) subset developed in IL-10-deficient mice, but this was blocked by treatment with antibody to transforming growth factor-beta. Thus, Foxp3(+) and Foxp3(-) precursor cells give rise to peripheral IL-10-expressing T(reg) cells by a mechanism dependent on transforming growth factor-beta and independent of IL-10.
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Samples were scored by a pathologist in a blinded fashion.
“Samples were scored by a pathologist in a blinded fashion as previously described (86).”
From T <sub>H</sub> 17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity (2020) · cites this paper as [86]
Cites
Control of Regulatory T Cell Development by the Transcription Factor <i>Foxp3</i>
Hori, S., Nomura, T., & Sakaguchi, S. (2003) · Science · doi:10.1126/science.1079490 · Cited by 8,187 · see citing works
Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., & Kuchroo, V. K. (2006) · Nature · doi:10.1038/nature04753 · Cited by 6,992 · see citing works
Interleukin-10 and the Interleukin-10 Receptor
Moore, K. W., de Waal Malefyt, R., Coffman, R. L., & O'Garra, A. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.683 · Cited by 6,737 · see citing works
Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M., & Toda, M. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.155.3.1151 · Cited by 5,608 · see citing works
Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M., & Stockinger, B. (2006) · Immunity · doi:10.1016/j.immuni.2006.01.001 · Cited by 3,605 · see citing works
Sellon, R. K., Tonkonogy, S., Schultz, M., Dieleman, L. A., Grenther, W., Balish, E., Rennick, D. M., & Sartor, R. B. (1998) · Infection and Immunity · doi:10.1128/iai.66.11.5224-5231.1998 · Cited by 1,483 · see citing works
Th17: An Effector CD4 T Cell Lineage with Regulatory T Cell Ties
Weaver, C. T., Harrington, L. E., Mangan, P. R., Gavrieli, M., & Murphy, K. M. (2006) · Immunity · doi:10.1016/j.immuni.2006.06.002 · Cited by 1,422 · see citing works
Self-citationPowrie, F., Leach, M. W., Mauze, S., Caddie, L. B., & Coffman, R. L. (1993) · International Immunology · doi:10.1093/intimm/5.11.1461 · Cited by 1,078 · see citing works
Marie, J. C., Liggitt, D., & Rudensky, A. Y. (2006) · Immunity · doi:10.1016/j.immuni.2006.07.012 · Cited by 480 · see citing works
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The gut microbiota--masters of host development and physiology
Sommer, F., & Bäckhed, F. (2013) · Nature Reviews Microbiology · doi:10.1038/nrmicro2974 · Cited by 3,681 · see citing works
Induction of Colonic Regulatory T Cells by Indigenous <i>Clostridium</i> Species
Atarashi, K., Tanoue, T., Shima, T., Imaoka, A., Kuwahara, T., Momose, Y., Cheng, G., Yamasaki, S., Saito, T., Ohba, Y., et al. (2011) · Science · doi:10.1126/science.1198469 · Cited by 3,752 · see citing works
Kaser, A., Zeissig, S., & Blumberg, R. S. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101225 · Cited by 1,806 · see citing works
Reciprocal interactions of the intestinal microbiota and immune system
Maynard, C. L., Elson, C. O., Hatton, R. D., & Weaver, C. T. (2012) · Nature · doi:10.1038/nature11551 · Cited by 1,598 · see citing works
Regulatory T Cell-Derived Interleukin-10 Limits Inflammation at Environmental Interfaces
Rubtsov, Y. P., Rasmussen, J. P., Chi, E. Y., Fontenot, J., Castelli, L., Ye, X., Treuting, P., Siewe, L., Roers, A., Henderson, W. R., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.02.017 · Cited by 1,586 · see citing works
Self-citationLate Developmental Plasticity in the T Helper 17 Lineage
Lee, Y. K., Turner, H., Maynard, C. L., Oliver, J. R., Chen, D., Elson, C. O., & Weaver, C. T. (2009) · Immunity · doi:10.1016/j.immuni.2008.11.005 · Cited by 1,053 · see citing works
Self-citationRegulation of the immune response by the aryl hydrocarbon receptor
Gutiérrez-Vázquez, C., & Quintana, F. J. (2018) · Immunity · doi:10.1016/j.immuni.2017.12.012 · Cited by 985 · see citing works
TGF-β Activation and Function in Immunity
Travis, M. A., & Sheppard, D. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120257 · Cited by 856 · see citing works
Intestinal Bacterial Colonization Induces Mutualistic Regulatory T Cell Responses
Geuking, M. B., Cahenzli, J., Lawson, M. A. E., Ng, D. C. K., Slack, E., Hapfelmeier, S., McCoy, K. D., & Macpherson, A. J. (2011) · Immunity · doi:10.1016/j.immuni.2011.03.021 · Cited by 840 · see citing works
The microbiome in infectious disease and inflammation
Honda, K., & Littman, D. R. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-074937 · Cited by 791 · see citing works
Development and maintenance of intestinal regulatory T cells
Tanoue, T., Atarashi, K., & Honda, K. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.36 · Cited by 553 · see citing works
Contextual Regulation of Inflammation: A Duet by Transforming Growth Factor-β and Interleukin-10
Li, M. O., & Flavell, R. A. (2008) · Immunity · doi:10.1016/j.immuni.2008.03.003 · Cited by 501 · see citing works
Hough, K. P., Curtiss, M. L., Blain, T. J., Liu, R.-M., Trevor, J., Deshane, J. S., & Thannickal, V. J. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.00191 · Cited by 432 · see citing works
Current status of interleukin-10 and regulatory T-cells in cancer
Dennis, K. L., Blatner, N. R., Gounari, F., & Khazaie, K. (2013) · Current Opinion in Oncology · doi:10.1097/cco.0000000000000006 · Cited by 289 · see citing works
Type 1 regulatory T cells (Tr1) in autoimmunity
Pot, C., Apetoh, L., & Kuchroo, V. K. (2011) · Seminars in Immunology · doi:10.1016/j.smim.2011.07.005 · Cited by 171 · see citing works
Harbour, S. N., DiToro, D. F., Witte, S. J., Zindl, C. L., Gao, M., Schoeb, T. R., Jones, G. W., Jones, S. A., Hatton, R. D., & Weaver, C. T. (2020) · Science Immunology · doi:10.1126/sciimmunol.aaw2262 · Cited by 151 · see citing works
Self-citationMaseda, D., Candando, K. M., Smith, S. H., Kalampokis, I., Weaver, C. T., Plevy, S. E., Poe, J. C., & Tedder, T. F. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300649 · Cited by 144 · see citing works
Self-citationEnhanced Th17 phenotype in individuals with generalized anxiety disorder
Vieira, M. M. M., Ferreira, T. B., Pacheco, P. A. F., Barros, P. O., Almeida, C. R. M., Araújo-Lima, C. F., Silva-Filho, R. G., Hygino, J., Andrade, R. M., Linhares, U. C., et al. (2010) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.07.018 · Cited by 118 · see citing works
Zhang, H., Madi, A., Yosef, N., Chihara, N., Awasthi, A., Pot, C., Lambden, C., Srivastava, A., Burkett, P. R., Nyman, J., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108433 · Cited by 91 · see citing works
Touch, S., Godefroy, E., Rolhion, N., Danne, C., Oeuvray, C., Straube, M., Galbert, C., Brot, L., Alonso Salgueiro, I., Chadi, S., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.154722 · Cited by 80 · see citing works
Linhares, U. C., Schiavoni, P. B., Barros, P. O., Kasahara, T. M., Teixeira, B., Ferreira, T. B., Alvarenga, R., Hygino, J., Vieira, M. M. M., Bittencourt, V. C. B., et al. (2013) · Journal of Clinical Immunology · doi:10.1007/s10875-012-9780-2 · Cited by 78 · see citing works
Hoffman, B. E., Martino, A. T., Sack, B. K., Cao, O., Liao, G., Terhorst, C., & Herzog, R. W. (2011) · Molecular Therapy · doi:10.1038/mt.2011.33 · Cited by 72 · see citing works
Rivino, L., Gruarin, P., Häringer, B., Steinfelder, S., Lozza, L., Steckel, B., Weick, A., Sugliano, E., Jarrossay, D., Kühl, A. A., et al. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20091021 · Cited by 64 · see citing works
Okamura, T., Yamamoto, K., & Fujio, K. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00340 · Cited by 41 · see citing works
- Authors
- Maynard, C. L., Harrington, L. E., Janowski, K. M., Oliver, J. R., Zindl, C. L., Rudensky, A. Y., & Weaver, C. T.
- Affiliations
- University of Alabama at Birmingham (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Weaver, Casey T
- Venue
- Nature Immunology
- Published
- 2007-08-12
- Volume
- 8
- Issue
- 9
- Pages
- 931-941
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2074006404
- Cited by
- 599
- References
- 9
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 16 · 2023: 28 · 2022: 25 · 2021: 29 · 2020: 38 · 2019: 31 · 2018: 21 · 2017: 22 · 2016: 37 · 2015: 35 · 2014: 34 · 2013: 37 · 2012: 42
- FWCI
- 16.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- regulatory T cells, IL-10, Foxp3, Treg differentiation, TGF-beta, immune homeostasis, IL-10-deficient mice
- MeSH terms
- Animals, Cell Differentiation, Flow Cytometry, Hematopoietic Stem Cells, Intestines, Mice, Inbred C57BL, Mice, Transgenic, Peyer's Patches, T-Lymphocyte Subsets, Transforming Growth Factor beta, Interleukin-10, T-Lymphocytes, Regulatory, Mice, Forkhead Transcription Factors
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