Zoned Out: Functional Mapping of Stromal Signaling Microenvironments in the Thymus
Abstract
All hematopoietic cells, including T lymphocytes, originate from stem cells that reside in the bone marrow. Most hematopoietic lineages also mature in the bone marrow, but in this respect, T lymphocytes differ. Under normal circumstances, most T lymphocytes are produced in the thymus from marrow-derived progenitors that circulate in the blood. Cells that home to the thymus from the marrow possess the potential to generate multiple T and non-T lineages. However, there is little evidence to suggest that, once inside the thymus, they give rise to anything other than T cells. Thus, signals unique to the thymic microenvironment compel multipotent progenitors to commit to the T lineage, at the expense of other potential lineages. Summarizing what is known about the signals the thymus delivers to uncommitted progenitors, or to immature T-committed progenitors, to produce functional T cells is the focus of this review.
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Notch ligands are the most important environmental signals thymus stroma provides to developing T cells across vertebrates.
“Notch ligands are the most important of all the environmental signals that the thymus stroma provides to developing T cells, apparently across all vertebrates (59–61)”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [60]
Following an unknown triggering signal, after a variable delay, cells in each cohort migrate centrifugally toward the outer thymic cortex, and cell surface marker expression patterns imply that lineage commitment occurs midway in this migration.
“Following an unknown triggering signal, after a variable delay (125), the cells in each cohort then begin to migrate centrifugally toward the outer thymic cortex, and cell surface marker expression patterns imply that it is somewhere midway in the course of this migration that the individual cells undergo lineage commitment [reviewed by (60, 130)].”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [60]
Cites
Cross-Presentation, Dendritic Cells, Tolerance and Immunity
Heath, W. R., & Carbone, F. R. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.47 · Cited by 882 · see citing works
Thymopoiesis independent of common lymphoid progenitors.
Allman, D., Sambandam, A., Kim, S., Miller, J. P., Pagan, A., Well, D., Meraz, A., & Bhandoola, A. (2003) · Nature Immunology · doi:10.1038/ni878 · Cited by 544 · see citing works
Sanna, M. G., Wang, S.-K., Gonzalez-Cabrera, P. J., Don, A., Marsolais, D., Matheu, M. P., Wei, S. H., Parker, I., Jo, E., Cheng, W.-C., et al. (2006) · Nature Chemical Biology · doi:10.1038/nchembio804 · Cited by 406 · see citing works
Wu, L., Li, C. L., & Shortman, K. (1996) · The Journal of experimental medicine · doi:10.1084/jem.184.3.903 · Cited by 400 · see citing works
Taghon, T., Yui, M. A., Pant, R., Diamond, R. A., & Rothenberg, E. V. (2006) · Immunity · doi:10.1016/j.immuni.2005.11.012 · Cited by 312 · see citing works
Porritt, H. E., Gordon, K., & Petrie, H. T. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030837 · Cited by 167 · see citing works
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Central CD4+ T cell tolerance: deletion versus regulatory T cell differentiation
Klein, L., Robey, E. A., & Hsieh, C.-S. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-018-0083-6 · Cited by 214 · see citing works
Yang, H., Youm, Y.-H., & Dixit, V. D. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900562 · Cited by 196 · see citing works
Savino, W., & Dardenne, M. (2010) · Proceedings of The Nutrition Society · doi:10.1017/s0029665110002545 · Cited by 109 · see citing works
Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development
Rothenberg, E. V., Hosokawa, H., & Ungerbäck, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00228 · Cited by 99 · see citing works
Belyaev, N. N., Biró, J., Athanasakis, D., Fernandez-Reyes, D., & Potocnik, A. J. (2012) · Immunogenetics · doi:10.1007/s00251-012-0620-6 · Cited by 24 · see citing works
- Authors
- Petrie, H. T., & Zúñiga-Pflücker, J. C.
- Affiliations
- Scripps Florida Research Institute, Jupiter, Florida 33458;
- Department of Immunology, University of Toronto and Sunnybrook Research Institute, Toronto, Ontario M4N 3M5, Canada;
- ORCID
- Petrie, Howard T.
- Venue
- Annual Review of Immunology
- Publisher
- Annual Reviews
- Published
- 2007-04-01
- Volume
- 25
- Issue
- 1
- Pages
- 649-679
- ISSN
- 0732-0582 (ISSN-L)
- 1545-3278
- OpenAlex
- W2134705919
- Cited by
- 454
- References
- 6
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 13 · 2023: 13 · 2022: 23 · 2021: 16 · 2020: 17 · 2019: 22 · 2018: 18 · 2017: 20 · 2016: 14 · 2015: 28 · 2014: 25 · 2013: 31 · 2012: 47
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- thymus, thymic microenvironment, stromal signaling, T cell development, thymocyte differentiation, T cell commitment, hematopoietic progenitor cells, thymic stroma, T cell selection
- MeSH terms
- Animals, Bone Marrow, Cell Differentiation, Cell Movement, Hematopoietic Stem Cells, Humans, T-Lymphocytes, Thymus Gland, Signal Transduction, Stromal Cells
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