A1 Refereed original research article in a scientific journal
Phenotypic profiling of human induced regulatory T cells at early differentiation : insights into distinct immunosuppressive potential
Authors: Kattelus, Roosa; Starskaia, Inna; Lindén, Markus; Batkulwar, Kedar; Pietilä, Sami; Moulder, Robert; Marson, Alexander; Rasool, Omid; Suomi, Tomi; Elo, Laura L.; Lahesmaa, Riitta; Buchacher, Tanja
Publisher: SPRINGER BASEL AG
Publishing place: BASEL
Publication year: 2024
Journal: Cellular and Molecular Life Sciences
Journal acronym: CELL MOL LIFE SCI
Article number: 399
Volume: 81
Issue: 1
Number of pages: 17
ISSN: 1420-682X
eISSN: 1420-9071
DOI: https://doi.org/10.1007/s00018-024-05429-3
Web address : https://link.springer.com/article/10.1007/s00018-024-05429-3
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/458300538
Regulatory T cells (Tregs) play a key role in suppressing systemic effector immune responses, thereby preventing autoimmune diseases but also potentially contributing to tumor progression. Thus, there is great interest in clinically manipulating Tregs, but the precise mechanisms governing in vitro-induced Treg (iTreg) differentiation are not yet fully understood. Here, we used multiparametric mass cytometry to phenotypically profile human iTregs during the early stages of in vitro differentiation at single-cell level. A panel of 25 metal-conjugated antibodies specific to markers associated with human Tregs was used to characterize these immunomodulatory cells. We found that iTregs highly express the transcription factor FOXP3, as well as characteristic Treg-associated surface markers (e.g. CD25, PD1, CD137, CCR4, CCR7, CXCR3, and CD103). Expression of co-inhibitory factors (e.g. TIM3, LAG3, and TIGIT) increased slightly at late stages of iTreg differentiation. Further, CD103 was upregulated on a subpopulation of iTregs with greater suppressive capacity than their CD103− counterparts. Using mass-spectrometry-based proteomics, we showed that sorted CD103+ iTregs express factors associated with immunosuppression. Overall, our study highlights that during early stages of differentiation, iTregs resemble memory-like Treg features with immunosuppressive activity, and provides opportunities for further investigation into the molecular mechanisms underlying Treg function.
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Funding information in the publication:
RL was supported by the Academy of Finland (AoF) grants 292335, 294337, 292482, 319280, 329277, 331793, 335435 and 31444; by grants from the JDRF; the Novo Nordisk Foundation (grant NNF19OC0057218); the Sigrid Jusélius Foundation; Jane and Aatos Erkko Foundation and the Finnish Cancer Foundation. LLE reports grants from the European Research Council ERC (677943), European Union’s Horizon 2020 research and innovation programme (955321), Academy of Finland (310561, 314443, 329278, 335434, 335611 and 341342), and Sigrid Juselius Foundation, during the conduct of the study. I.S. was supported by Turku Doctoral Programme of Molecular Medicine (TuDMM), Finnish Diabetes Research Foundation, InFLAMES Flagship Programme of the Academy of Finland, Diabetes Wellness Suomi, Finnish Cultural Foundation. KB was supported by Finnish Diabetes Research Foundation, Finnish Cultural Foundation and Orion Research Foundation. Our research is also supported by University of Turku, Åbo Akademi University, Turku Doctoral Programme of Molecular Medicine (TuDMM), InFLAMES Flagship Programme of the Academy of Finland (decision number: 337530), Biocenter Finland, and ELIXIR Finland. Figure 1A was created with BioRender.com. Open Access funding provided by University of Turku (including Turku University Central Hospital).
