Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages
Open accessAbstract
After activation, CD4(+) helper T (Th) cells differentiate into distinct effector subsets. Although chemokine (C-X-C motif) receptor 5-expressing T follicular helper (Tfh) cells are important in humoral immunity, their developmental regulation is unclear. Here we show that Tfh cells had a distinct gene expression profile and developed in vivo independently of the Th1 or Th2 cell lineages. Tfh cell generation was regulated by ICOS ligand (ICOSL) expressed on B cells and was dependent on interleukin-21 (IL-21), IL-6, and signal transducer and activator of transcription 3 (STAT3). However, unlike Th17 cells, differentiation of Tfh cells did not require transforming growth factor beta (TGF-beta) or Th17-specific orphan nuclear receptors RORalpha and RORgamma in vivo. Finally, naive T cells activated in vitro in the presence of IL-21 but not TGF-beta signaling preferentially acquired Tfh gene expression and promoted germinal-center reactions in vivo. This study thus demonstrates that Tfh is a distinct Th cell lineage.
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TFH cells are distinct from conventional CD4 cells.
“TFH cells are thought to be distinct from conventional CD4 cells (Nurieva et al., 2008; Nurieva et al., 2009)”
From Distinct characteristics of hippocampal pathogenic th17 cells in a mouse model of depression (2018) · cites this paper as Nurieva et al., 2008
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- Authors
- Nurieva, R. I., Chung, Y., Hwang, D., Yang, X. O., Kang, H. S., Ma, L., Wang, Y.-H., Watowich, S. S., Jetten, A. M., Tian, Q., & Dong, C.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Pohang University of Science and Technology (KR)
- National Institutes of Health (US)
- Institute for Systems Biology (US)
- Corresponding author
- Nurieva, Roza I.
- Dong, Chen
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 29
- Issue
- 1
- Pages
- 138-149
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC2556461
- OpenAlex
- W1987076250
- Cited by
- 1,205
- References
- 8
- Citations by year
- 2026: 29 · 2025: 28 · 2024: 38 · 2023: 40 · 2022: 46 · 2021: 65 · 2020: 66 · 2019: 66 · 2018: 78 · 2017: 59 · 2016: 82 · 2015: 80 · 2014: 76 · 2013: 96 · 2012: 93
- FWCI
- 36.58
- Type
- journal article
- Language
- en
- Update notices
- erratum (2008-08-15)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Open Access System for Information Sharing (Pohang University of Science and Technology) (submittedVersion)
- Funders
- National Institutes of Health (Z01-ES-101586)
- National Institute of Allergy and Infectious Diseases (R01AI050761, R56AI050761, R01AI050746, R01AI054912)
- National Institute of Environmental Health Sciences (Z01ES101586)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR050772)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- T follicular helper cells, IL-21, ICOS ligand, Th1 differentiation, Th2 differentiation, Th17 cell differentiation, STAT3 signaling, interleukin-6, TGF-beta, RORα, RORγ, naive T cell activation, germinal center, humoral immunity, CD4+ T helper cells
- MeSH terms
- Interleukin-21, Animals, B-Lymphocytes, Cell Differentiation, Flow Cytometry, T-Lymphocytes, Helper-Inducer, Immunohistochemistry, Interleukins, Lymphocyte Activation, Mice, Mutant Strains, Proteins, Signal Transduction, Interleukin-6, Gene Expression, T-Lymphocyte Subsets, Transforming Growth Factor beta, Germinal Center, Cell Lineage, Adoptive Transfer, Reverse Transcriptase Polymerase Chain Reaction, Interleukin-17, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, STAT3 Transcription Factor, Mice, Inducible T-Cell Co-Stimulator Ligand
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