Blimp‐1 induces and Hobit maintains the cytotoxic mediator granzyme B in CD8 T cells
Open accessAbstract
CD8 T cells acquire cytotoxic molecules including granzyme B during effector differentiation. Both tissue‐resident memory CD8 T cells (Trm) and circulating CD45RA+ effector‐type T cells (Temra) cells have the ability to retain granzyme B protein expression into the memory phase, but it is unclear how this persistence of cytolytic activity is regulated during steady state. Previously, we have described that the transcriptional regulators Hobit and Blimp‐1 have overlapping target genes that include granzyme B, but their impact on the regulation of cytotoxicity in Trm and Temra cells during homeostasis has remained unclear. We examined the expression regulation of Hobit and Blimp‐1 in murine and human CD8 T‐cells to determine their timeframe of activity. While Blimp‐1 mRNA was expressed throughout effector and memory T cells, Blimp‐1 protein, was only transiently expressed during the effector stage. In contrast, Hobit mRNA and protein expression was stably maintained during quiescence, but downregulated after activation. Notably, Blimp‐1 was required for expression of granzyme B in murine effector T cells and Trm, while Hobit specifically regulated granzyme B in murine Trm during the memory phase. These findings suggest that Blimp‐1 initiates cytotoxic effector function and that Hobit maintains cytotoxicity in a deployment‐ready modus in Trm.
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Both Trm subsets from HFHC mice and RES mice expressed core signature genes of Trm, with exceptions including Itgae (CD103) and Eomes.
“Furthermore, bulk RNA-seq analysis of isolated cells (ND naïve, HFHC Tem, HFHC Trm, and RES Trm) revealed that both Trm subsets from HFHC mice and RES mice expressed core signature genes of Trm21–24 with exceptions including Itgae (CD103) and Eomes (Fig. 4d).”
From CD8+ tissue-resident memory T cells promote liver fibrosis resolution by inducing apoptosis of hepatic stellate cells (2021) · cites this paper as [22]
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- Authors
- Kragten, N. A. M., Behr, F. M., Vieira Braga, F. A., Remmerswaal, E. B. M., Wesselink, T. H., Oja, A. E., Hombrink, P., Kallies, A., van Lier, R. A. W., Stark, R., & van Gisbergen, K. P. J. M.
- Affiliations
- Sanquin (NL)
- Dept of Hematopoiesis Sanquin Research and Landsteiner Laboratory Amsterdam UMC University of Amsterdam Amsterdam Netherlands
- Amsterdam University Medical Centers (NL)
- The University of Melbourne (AU)
- ORCID
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2018-08-16
- Volume
- 48
- Issue
- 10
- Pages
- 1644-1662
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W2884205201
- Cited by
- 91
- References
- 51
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 11 · 2023: 10 · 2022: 20 · 2021: 13 · 2020: 9 · 2019: 7 · 2018: 2
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- ZonMw (VENI # 016.186.116, VIDI # 016.136.338)
- Landsteiner Foundation for Blood Transfusion Research (Fellowship # 1629)
- 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 › Immune Cell Function and Interaction
- Keywords
- Blimp-1, Hobit, granzyme B, CD8+ T cells, tissue-resident memory T cells, effector memory T cells, cytotoxicity, transcriptional regulation, T cell homeostasis, transcription factors
- MeSH terms
- Positive Regulatory Domain I-Binding Factor 1, Animals, Cells, Cultured, Gene Expression Regulation, Humans, Immunologic Memory, Mice, Inbred C57BL, Transcription Factors, Mice, Knockout, CD8-Positive T-Lymphocytes, Mice, Granzymes, Natural Killer T-Cells
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