Journal of Molecular Medicine

, 86:1139 | Cite as

Critical immunological pathways are downregulated in APECED patient dendritic cells

  • Nora Pöntynen
  • Mari Strengell
  • Niko Sillanpää
  • Juha Saharinen
  • Ismo Ulmanen
  • Ilkka Julkunen
  • Leena Peltonen
Original Article


Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) is a monogenic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. AIRE functions as a transcriptional regulator, and it has a central role in the development of immunological tolerance. AIRE regulates the expression of ectopic antigens in epithelial cells of the thymic medulla and has been shown to participate in the development of peripheral tolerance. However, the mechanism of action of AIRE has remained elusive. To further investigate the role of AIRE in host immune functions, we studied the properties and transcript profiles in in vitro monocyte-differentiated dendritic cells (moDCs) obtained from APECED patients and healthy controls. AIRE-deficient monocytes showed typical DC morphology and expressed DC marker proteins cluster of differentiation 86 and human leukocyte antigen class II. APECED patient-derived moDCs were functionally impaired: the transcriptional response of cytokine genes to pathogens was drastically reduced. Interestingly, some changes were observable already at the immature DC stage. Pathway analyses of transcript profiles revealed that the expression of the components of the host cell signaling pathways involved in cell–cell signalling, innate immune responses, and cytokine activity were reduced in APECED moDCs. Our observations support a role for AIRE in peripheral tolerance and are the first ones to show that AIRE has a critical role in DC responses to microbial stimuli in humans.


AIRE APS1 Dendritic cell Transcript profile 



We thank Drs. T. Petteri Arstila and Jaakko Perheentupa for the help in obtaining the patient samples. Sampo Sammalisto and Samuli Ripatti are acknowledged for helping with the statistical analysis, and T. Petteri Arstila and Seppo Meri are thanked for critical reading of the manuscript. Lea Puhakka and Anne Vikman are thanked for the diligent technical assistance. Pamela Österlund and the other members of the Julkunen group are warmly thanked for help in their laboratory.


This study was supported by the Magnus Ehrnrooth foundation, Helsinki Biomedical Graduate School in (HBGS), EU FP6 program project EURAPS, the Center of Excellence in Disease Genetics of the Academy of Finland, Academy of Finland (grant 206282), and The Lilly Foundation (Finland).

Conflict of interest statement

The authors have no conflicting financial interest, connections, or other conflicting situations regarding this manuscript.

Supplementary material

109_2008_374_MOESM1_ESM.xls (194 kb)
ESM 1 Supplemental data (XLS 198 KB).


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Nora Pöntynen
    • 1
  • Mari Strengell
    • 2
  • Niko Sillanpää
    • 3
  • Juha Saharinen
    • 1
    • 4
  • Ismo Ulmanen
    • 1
  • Ilkka Julkunen
    • 2
  • Leena Peltonen
    • 1
    • 5
    • 6
    • 7
  1. 1.National Public Health Institute and FIMMInstitute for Molecular Medicine Finland, BiomedicumHelsinkiFinland
  2. 2.Department of Viral Diseases and ImmunologyNational Public Health InstituteHelsinkiFinland
  3. 3.Department of Pathology, Institute of Medical Technology, Tampere University HospitalUniversity of TampereTampereFinland
  4. 4.Genome Informatics UnitBiomedicumHelsinkiFinland
  5. 5.Department of Medical GeneticsUniversity of HelsinkiHelsinkiFinland
  6. 6.Wellcome Trust Sanger InstituteCambridgeUK
  7. 7.The Broad InstituteCambridgeUSA

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