Single cell characterization of blood and expanded regulatory T cells in autoimmune polyendocrine syndrome type 1
Thea Sjøgren,
Shahinul Islam,
Igor Filippov,
Adrianna Jebrzycka,
André Sulen,
Lars E. Breivik,
Alexander Hellesen,
Anders P. Jørgensen,
Kari Lima,
Liina Tserel,
Kai Kisand,
Pärt Peterson,
Annamari Ranki,
Eystein S. Husebye,
Bergithe E. Oftedal,
Anette S.B. Wolff
Affiliations
Thea Sjøgren
Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, Bergen, Norway
Shahinul Islam
Department of Medicine, Haukeland University Hospital, Bergen, Norway
Igor Filippov
QIAGEN Aarhus A/S, Aarhus, Denmark; Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
Adrianna Jebrzycka
Department of Clinical Science, University of Bergen, Bergen, Norway
André Sulen
Department of Clinical Science, University of Bergen, Bergen, Norway
Lars E. Breivik
Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, Bergen, Norway
Alexander Hellesen
Department of Clinical Science, University of Bergen, Bergen, Norway
Anders P. Jørgensen
Department of Endocrinology, Oslo University Hospital, Oslo, Norway
Kari Lima
Department of Medicine, Akershus University Hospital, Lørenskog, Norway
Liina Tserel
Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
Kai Kisand
Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
Pärt Peterson
Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
Annamari Ranki
Department of Dermatology, Allergology and Venereology, University of Helsinki and Helsinki University Hospital, Inflammation Centre, Helsinki, Finland
Eystein S. Husebye
Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, Bergen, Norway
Bergithe E. Oftedal
Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, Bergen, Norway
Anette S.B. Wolff
Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, Bergen, Norway; Corresponding author
Summary: 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.
