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

doi:10.1016/j.isci.2024.109610

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

iScience. 2024 Mar 27;27(4):109610. doi: 10.1016/j.isci.2024.109610. eCollection 2024 Apr 19.

Authors

Thea Sjøgren^{1

2}, Shahinul Islam², Igor Filippov^{3

4}, Adrianna Jebrzycka¹, André Sulen¹, Lars E Breivik^{1

2}, Alexander Hellesen¹, Anders P Jørgensen⁵, Kari Lima⁶, Liina Tserel⁴, Kai Kisand⁴, Pärt Peterson⁴, Annamari Ranki⁷, Eystein S Husebye^{1

2}, Bergithe E Oftedal^{1

2}, Anette S B Wolff^{1

2}

Affiliations

¹ Department of Clinical Science, University of Bergen, Bergen, Norway.
² Department of Medicine, Haukeland University Hospital, Bergen, Norway.
³ QIAGEN Aarhus A/S, Aarhus, Denmark.
⁴ Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
⁵ Department of Endocrinology, Oslo University Hospital, Oslo, Norway.
⁶ Department of Medicine, Akershus University Hospital, Lørenskog, Norway.
⁷ Department of Dermatology, Allergology and Venereology, University of Helsinki and Helsinki University Hospital, Inflammation Centre, Helsinki, Finland.

Abstract

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.

Keywords: Components of the immune system; Health sciences; Immunology; Proteomics; Transcriptomics.