Single cell characterization of blood and expanded regulatory T cells in autoimmune polyendocrine syndrome type 1.

Autor: Sjøgren T; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Medicine, Haukeland University Hospital, Bergen, Norway., Islam S; Department of Medicine, Haukeland University Hospital, Bergen, Norway., Filippov I; QIAGEN Aarhus A/S, Aarhus, Denmark.; Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia., Jebrzycka A; Department of Clinical Science, University of Bergen, Bergen, Norway., Sulen A; Department of Clinical Science, University of Bergen, Bergen, Norway., Breivik LE; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Medicine, Haukeland University Hospital, Bergen, Norway., Hellesen A; Department of Clinical Science, University of Bergen, Bergen, Norway., Jørgensen AP; Department of Endocrinology, Oslo University Hospital, Oslo, Norway., Lima K; Department of Medicine, Akershus University Hospital, Lørenskog, Norway., Tserel L; Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia., Kisand K; Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia., Peterson P; Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia., Ranki A; Department of Dermatology, Allergology and Venereology, University of Helsinki and Helsinki University Hospital, Inflammation Centre, Helsinki, Finland., Husebye ES; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Medicine, Haukeland University Hospital, Bergen, Norway., Oftedal BE; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Medicine, Haukeland University Hospital, Bergen, Norway., Wolff ASB; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Medicine, Haukeland University Hospital, Bergen, Norway.
Jazyk: angličtina
Zdroj: IScience [iScience] 2024 Mar 27; Vol. 27 (4), pp. 109610. Date of Electronic Publication: 2024 Mar 27 (Print Publication: 2024).
DOI: 10.1016/j.isci.2024.109610
Abstrakt: Immune tolerance fails in autoimmune polyendocrine syndrome type 1 (APS-1) because of AIRE mutations. We have used single cell transcriptomics to characterize regulatory T cells (Tregs) sorted directly from blood and from in vitro expanded Tregs in APS-1 patients compared to healthy controls. We revealed only CD52 and LTB (down) and TXNIP (up) as consistently differentially expressed genes in the datasets. There were furthermore no large differences of the TCR-repertoire of expanded Tregs between the cohorts, but unique patients showed a more restricted use of specific clonotypes. We also found that in vitro expanded Tregs from APS-1 patients had similar suppressive capacity as controls in co-culture assays, despite expanding faster and having more exhausted cells. Our results suggest that APS-1 patients do not have intrinsic defects in their Treg functionality, and that their Tregs can be expanded ex vivo for potential therapeutic applications.
Competing Interests: The authors declare no competing interests.
(© 2024 The Author(s).)
Databáze: MEDLINE