Maturing Human CD127+ CCR7+ PDL1+ Dendritic Cells Express AIRE in the Absence of Tissue Restricted Antigens.
Fergusson, Joannah R
Heesters, Balthasar A
van Unen, Vincent
van Hamburg, Jan Piet
van der Wel, Nicole N
Tas, Sander W
Anderson, Mark S
Holländer, Georg A
Frontiers in Immunology
MetadataShow full item record
Fergusson, J. R., Morgan, M., Bruchard, M., Huitema, L., Heesters, B. A., van Unen, V., van Hamburg, J. P., et al. (2019). Maturing Human CD127+ CCR7+ PDL1+ Dendritic Cells Express AIRE in the Absence of Tissue Restricted Antigens.. Frontiers in Immunology, 9 (2902)https://doi.org/10.3389/fimmu.2018.02902
Expression of the Autoimmune regulator (AIRE) outside of the thymus has long been suggested in both humans and mice, but the cellular source in humans has remained undefined. Here we identify AIRE expression in human tonsils and extensively analyzed these "extra-thymic AIRE expressing cells" (eTACs) using combinations of flow cytometry, CyTOF and single cell RNA-sequencing. We identified AIRE+ cells as dendritic cells (DCs) with a mature and migratory phenotype including high levels of antigen presenting molecules and costimulatory molecules, and specific expression of CD127, CCR7, and PDL1. These cells also possessed the ability to stimulate and re-stimulate T cells and displayed reduced responses to toll-like receptor (TLR) agonists compared to conventional DCs. While expression of AIRE was enriched within CCR7+CD127+ DCs, single-cell RNA sequencing revealed expression of AIRE to be transient, rather than stable, and associated with the differentiation to a mature phenotype. The role of AIRE in central tolerance induction within the thymus is well-established, however our study shows that AIRE expression within the periphery is not associated with an enriched expression of tissue-restricted antigens (TRAs). This unexpected finding, suggestive of wider functions of AIRE, may provide an explanation for the non-autoimmune symptoms of APECED patients who lack functional AIRE.
AIRE, PDL1, dendritic cells, maturation, tissue restricted antigen
JF and HS were funded by project ERC-2013-ADG number 341038. MB was funded by EMBO ALTF 786-2013. BH was supported by the Netherlands Organization for Scientific Research (NWO) Veni program (91618032). LH, JpvH, and ST were supported by a grant from the Dutch Arthritis Foundation (2013_2_37). MM was supported by Wellcome Trust (grant105045/Z/14/Z). JM was supported by core funding from the European Molecular Biology Laboratory and from Cancer Research UK (award number 17197).
Cancer Research UK (C14303_do not transfer)
External DOI: https://doi.org/10.3389/fimmu.2018.02902
This record's URL: https://www.repository.cam.ac.uk/handle/1810/291178
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/