The transcription factors Blimp-1 and IRF4 jointly control the differentiation and function of effector regulatory T cells
Abstract
Regulatory T cells (T(reg) cells) are required for peripheral tolerance. Evidence indicates that T(reg) cells can adopt specialized differentiation programs in the periphery that are controlled by transcription factors usually associated with helper T cell differentiation. Here we demonstrate that expression of the transcription factor Blimp-1 defined a population of T(reg) cells that localized mainly to mucosal sites and produced IL-10. Blimp-1 was required for IL-10 production by these cells and for their tissue homeostasis. We provide evidence that the transcription factor IRF4, but not the transcription factor T-bet, was essential for Blimp-1 expression and for the differentiation of all effector T(reg) cells. Thus, our study defines a differentiation pathway that leads to the acquisition of T(reg) cell effector functions and requires both IRF4 and Blimp-1.
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Among RECs, aTregs displayed elevated activity of regulons corresponding to Foxp3, NF-κB TF family (Nfkb1, Nfkb2, Rel, Relb), Irf4, and Maf, previously associated with activation phenotype of Tregs.
“Among the RECs, the aTregs subset displayed elevated activity of the regulons corresponding to Foxp3, nuclear factor κB (NF-κB) TF family (Nfkb1, Nfkb2, Rel, and Relb), Irf4, and Maf, which were previously associated with activation phenotype of Tregs [Fig. 5B; (46, 47)].”
From Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes (2019) · cites this paper as [46]
An increasing list of transcription factors, including IRF4, STAT3, T-bet, GATA3, Bcl-6, and Blimp-1, regulate both effector T cell function and regulatory T cell function.
“an increasing list of transcription factors now shown to regulate both effector T cell function and regulatory T cell function, including IRF4, STAT3, T-bet, GATA3, Bcl-6, and Blimp-1 [98–105].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [103]
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Self-citation
- Authors
- Cretney, E., Xin, A., Shi, W., Minnich, M., Masson, F., Miasari, M., Belz, G. T., Smyth, G. K., Busslinger, M., Nutt, S. L., & Kallies, A.
- Affiliations
- Walter and Eliza Hall Institute of Medical Research (AU)
- The University of Melbourne (AU)
- Research Institute of Molecular Pathology (AT)
- Corresponding author
- Nutt, Stephen L
- Kallies, Axel
- ORCID
- Venue
- Nature Immunology
- Published
- 2011-03-06
- Volume
- 12
- Issue
- 4
- Pages
- 304-311
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2011873300
- Cited by
- 605
- References
- 65
- Citations by year
- 2026: 20 · 2025: 29 · 2024: 41 · 2023: 39 · 2022: 59 · 2021: 49 · 2020: 48 · 2019: 45 · 2018: 26 · 2017: 42 · 2016: 31 · 2015: 50 · 2014: 46 · 2013: 32 · 2012: 37
- FWCI
- 17.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- 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, Blimp-1, IRF4, T-bet, transcription factors, IL-10 production, effector regulatory T cells, Treg differentiation, tissue homeostasis, peripheral tolerance, transcriptional regulation
- MeSH terms
- Positive Regulatory Domain I-Binding Factor 1, Interferon Regulatory Factor-4, Animals, Base Sequence, Binding Sites, Cell Differentiation, Cells, Cultured, Flow Cytometry, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Protein Binding, Regulatory Sequences, Nucleic Acid, Sequence Homology, Nucleic Acid, Transcription Factors, Interleukin-10, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Green Fluorescent Proteins, T-Lymphocytes, Regulatory, Interferon Regulatory Factors, Mice
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