The DOI matches its Crossref record; 218 of the 218 references it cites were found in a registry or an index.
Helper T cell differentiation
Open accessAbstract
CD4+ T helper cells are key regulators of host health and disease. In the original model, specialized subsets of T helper cells are generated following activation through lineage-specifying cytokines and transcriptional programs, but recent studies have revealed increasing complexities for CD4+ T-cell differentiation. Here, we first discuss CD4+ T-cell differentiation from a historical perspective by highlighting the major studies that defined the distinct subsets of T helper cells. We next describe the mechanisms underlying CD4+ T-cell differentiation, including cytokine-induced signaling and transcriptional networks. We then review current and emerging topics of differentiation, including the plasticity and heterogeneity of T cells, the tissue-specific effects, and the influence of cellular metabolism on cell fate decisions. Importantly, recent advances in cutting-edge approaches, especially systems biology tools, have contributed to new concepts and mechanisms underlying T-cell differentiation and will likely continue to advance this important research area of adaptive immunity.
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“However, the current view is that CD4 Th cell subsets are not separate lineages but have plasticity and form a continuum of mixed functional capacities [177, 178].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [178]
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Citations
Cites
Control of Regulatory T Cell Development by the Transcription Factor Foxp3
Hori, S., Nomura, T., & Sakaguchi, S. (2003) · Science · doi:10.1126/science.1079490 · Cited by 8,187
Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
Fontenot, J. D., Gavin, M. A., & Rudensky, A. Y. (2003) · Nature Immunology · doi:10.1038/ni904 · Cited by 7,745
Mosmann, T. R., Cherwinski, H. M., Bond, M. W., Giedlin, M. A., & Coffman, R. L. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.136.7.2348 · Cited by 7,553
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
Park, J., Adoro, S., Guinter, T. I., Erman, B., Alag, A., Catálfamo, M., Kimura, M. Y., Cui, Y., Lucas, P. J., Gress, R. E., et al. (2010) · Nature Immunology · doi:10.1038/ni.1840 · Cited by 5,835
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
Ivanov, I. I., McKenzie, B. S., Zhou, L., Tadokoro, C. E., Lepelley, A., Lafaille, J. J., Cua, D. J., & Littman, D. R. (2006) · Cell · doi:10.1016/j.cell.2006.07.035 · Cited by 5,145
Harrington, L. E., Hatton, R. D., Mangan, P. R., Turner, H., Murphy, T. L., Murphy, K. M., & Weaver, C. T. (2005) · Nature Immunology · doi:10.1038/ni1254 · Cited by 4,742
Chen, W., Jin, W., Hardegen, N. J., Lei, K.-J., Li, L., Marinos, N. J., McGrady, G., & Wahl, S. M. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030152 · Cited by 4,678
A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
Park, H., Li, Z., Yang, X. O., Chang, S. H., Nurieva, R., Wang, Y.-H., Wang, Y., Hood, L., Zhu, Z., Tian, Q., et al. (2005) · Nature Immunology · doi:10.1038/ni1261 · Cited by 4,265
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Pahl, M. C., Sharma, P. K., Thomas, R. M., Thompson, Z., Mount, Z., Pippin, J. A., Morawski, P. A., Sun, P., Su, C., Campbell, D., et al. (2024) · eLife · doi:10.7554/elife.96852.2 · Cited by 1
Huoman, J. (2020) · Linköping University medical dissertations · doi:10.3384/diss.diva-170575
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de Assunção, S. F. (2020) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.17.2020.tde-04012021-102752
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Polevshchikov, A. V., & Nazarov, P. G. (2021) · Advances in Gerontology · doi:10.1134/s2079057021030103
Middleton, D. D. (2021) · The Research Repository @ WVU (West Virginia University) · doi:10.33915/etd.8292
Updates on Severe Combined Immunodeficiency
Cossu, F. (2022) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9789815039658122010015
Faculty Opinions recommendation of Signaling networks in immunometabolism.
Kane, L. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.737610223.793578145
Triviño, J. Y. M. (2020) · Repositorio Institucional (Pontificia Universidad Javeriana) · doi:10.11144/javeriana.10554.49675
General and Emerging Concepts of Immunity
Iborra, S., & Hidalgo, A. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821618-7.00263-7
dos Santos, B. R. C., dos Santos, A. C. M., Bastos, D. M., Santos, L. D. S., Praxedes, F. A. D. S., Tanabe, I. S. B., de Farias, K. F., & Figueiredo, E. V. M. D. S. (2022) · Immunological Investigations · doi:10.1080/08820139.2022.2140671
Topol, I. A., Polyakova, I. S., Elykova, A. V., & Kamyshny, A. М. (2022) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s002209302205026x
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刘, 艳. (2023) · Advances in Clinical Medicine · doi:10.12677/acm.2023.132285
Dinh, T. T. H. (2020) · Chula Digiverse · doi:10.58837/chula.the.2020.309
Wells, A. D., Pahl, M. C., Sharma, P. K., Thomas, R. M., Thompson, Z., Mount, Z., Pippin, J. A., Morawski, P. A., Campbell, D., Grant, S. F. A., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-2855977/v1
Pinamonti, V., Fuentes, A. M., Schmid, T., Cetin, M., Lerner, T., Hernandez, M. H., & Lindner, J. M. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.22.546056
Velasco, J. C. Z. (2023) · UVaDOC UVaDOC University of Valladolid Documentary Repository (University of Valladolid) · doi:10.35376/10324/61888
Almeida, L. K. Y. (2023) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.58.2023.tde-10112023-173334
Okuma, H. S., Watanabe, K., Tsuchihashi, K., Machida, R., Sadachi, R., Hirakawa, A., Ariyama, H., Kanai, M., Kamikura, M., Anjo, K., et al. (2023) · doi:10.1158/1078-0432.c.6982803.v1
Okuma, H. S., Watanabe, K., Tsuchihashi, K., Machida, R., Sadachi, R., Hirakawa, A., Ariyama, H., Kanai, M., Kamikura, M., Anjo, K., et al. (2023) · doi:10.1158/1078-0432.c.6982803
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韩, 登. (2024) · Advances in Clinical Medicine · doi:10.12677/acm.2024.1451517
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Miyajima, H., Fujita, Y., & Yamashita, T. (2024) · Springer eBooks · doi:10.1007/978-3-031-24297-7_2-1
Pahl, M. C., Sharma, P. K., Thomas, R. M., Thompson, Z., Mount, Z., Pippin, J. A., Morawski, P. A., Sun, P., Su, C., Campbell, D., et al. (2024) · eLife · doi:10.7554/elife.96852.2.sa0
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Badiola, I. (2024) · Advances in genetics · doi:10.1016/bs.adgen.2024.08.001
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Xiang, J., Leary, S. C., Wu, Z., & Yu, M. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1463399
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Miyajima, H., Fujita, Y., & Yamashita, T. (2024) · Springer eBooks · doi:10.1007/978-3-031-60006-7_2
Jang, S.-Y., Yi, S.-H., Song, H.-A., Park, M., Chung, K., Lee, J. K., Choi, J. W., Song, N., Rhee, Y. K., & Lee, K. (2025) · Food Science and Human Wellness · doi:10.26599/fshw.2025.9250476
Lê, T. T. V., Phan, T. L., Hồ, T. D., Lê, Đ. P., & Phạm, H. S. H. (2025) · Can Tho University Journal of Science · doi:10.22144/ctujos.2025.002
Zhao, W., Du, J., Su, J. E., Gao, J., Bai, H., Lv, D., Chen, X., Liu, D., Wang, G., & Xue, Q. (2025) · Virology · doi:10.1016/j.virol.2025.110496
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Omelchenko, A. A., Rahman, S. A., Viswanadham, V., Yuen, G. J., Estrada, P. M. D. R., D’Onofrio, V., Chen, Y., Sun, N., Mattoo, H., Varma, C. G., et al. (2026) · The Journal of Immunology · doi:10.1093/jimmun/vkag141.968
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Chen, Y., Wang, W., Xia, X., Xu, X., & Wang, S. (2025) · Journal of Immunology Research · doi:10.1155/jimr/9247816
Niu, S., Cai, L., Tao, X., Wang, X., Zhang, X., Li, Y., He, B., Tian, J., Zhang, Z., & Yang, Y. (2025) · Future Virology · doi:10.1080/17460794.2025.2574720
Zhang, W., Wang, G., Wang, Z., Zhou, G., & Jiang, H. (2025) · Analytical Biochemistry · doi:10.1016/j.ab.2025.116007
Zhang, X., Deng, X., Wu, X., Xu, Z., Feng, T., & Xu, J. (2025) · MarineMedicine · doi:10.64187/mm.2025010103
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Morone, D., Raimondi, A., & Molinari, M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.25.690386
Zhang, J., Diao, X., Jiang, Y., Chen, Y., Lai, C., Huang, C., Zhu, C., & Yong, Q. (2025) · Poultry Science · doi:10.1016/j.psj.2025.106218
Vinkel, J., Rib, L., Buil, A., Hedetoft, M., & Hyldegaard, O. (2024) · Figshare · doi:10.6084/m9.figshare.26638179
Vinkel, J., Rib, L., Buil, A., Hedetoft, M., & Hyldegaard, O. (2024) · Figshare · doi:10.6084/m9.figshare.26638182
Yang, F., Leyu, Z., Shen, Y., Wang, X., Fan, X., & Yang, L. (2024) · Figshare · doi:10.6084/m9.figshare.26687019
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Akhter, W., Nakhle, J., Vaillant, L., Garcin, G., Saout, C. L., Simon, M., Crozet, C., Djouad, F., Jørgensen, C., Vignais, M., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22598849
Wang, C., Liu, S., Zhang, X., Wang, Y., Guan, P., Bu, F., Wang, H., Wang, D., Fan, Y., Hou, S., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19753212
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Durand, M. (2021) · theses.fr (ABES) · doi:10.70675/2351c82ezd964z40edz8084z776fd97e6480
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Bergamaschi, L., Percio, S., Zhu, Y., Tinè, G., Miceli, R., Fiore, M., Palassini, E., Collini, P., Perrone, F., Rini, F., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.16.718860
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Chen, G., Zhao, C., Wang, C., Chen, G., Shi, J., & Chen, H. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.116781
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Omelchenko, A. A., Rahman, S. A., Wang, A., Tabib, T., Viswanadham, V., Yuen, G. J., Estrada, P. M. D. R., D’Onofrio, V., Chen, Y., Sun, N., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-75559-8
Zhou, J., Han, R., & Gao, T. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1890822
Metadata
- Authors
- Saravia, J., Chapman, N. M., & Chi, H.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Chi, Hongbo
- Venue
- Cellular & Molecular Immunology
- Published
- 2019-03-12
- Volume
- 16
- Issue
- 7
- Pages
- 634-643
- ISSN
- 1672-7681 (ISSN-L)
- 2042-0226
- PMC
- PMC6804569
- OpenAlex
- W2921191661
- Cited by
- 489
- References
- 218
- Citations by year
- 2026: 33 · 2025: 85 · 2024: 114 · 2023: 94 · 2022: 80 · 2021: 44 · 2020: 34 · 2019: 5
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cellular and Molecular Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Foundation for the National Institutes of Health
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- CD4+ T helper cells, T helper cell differentiation, T helper cell subsets, transcriptional regulatory networks, T cell plasticity, T cell heterogeneity, cellular metabolism, cell fate determination, systems biology
- MeSH terms
- Animals, Cell Differentiation, T-Lymphocytes, Helper-Inducer, Humans, Cytokines, Cell Lineage, Gene Regulatory Networks, Adaptive Immunity
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