RGD Reference Report - Breakdown of Immune Tolerance in AIRE-Deficient Rats Induces a Severe Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy-like Autoimmune Disease. - Rat Genome Database

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Breakdown of Immune Tolerance in AIRE-Deficient Rats Induces a Severe Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy-like Autoimmune Disease.

Authors: Ossart, Jason  Moreau, Anne  Autrusseau, Elodie  Ménoret, Séverine  Martin, Jérôme C  Besnard, Marine  Ouisse, Laure-Hélène  Tesson, Laurent  Flippe, Léa  Kisand, Kai  Peterson, Pärt  Hubert, François-Xavier  Anegon, Ignacio  Josien, Régis  Guillonneau, Carole 
Citation: Ossart J, etal., J Immunol. 2018 Aug 1;201(3):874-887. doi: 10.4049/jimmunol.1701318. Epub 2018 Jun 29.
RGD ID: 38599145
Pubmed: PMID:29959280   (View Abstract at PubMed)
DOI: DOI:10.4049/jimmunol.1701318   (Journal Full-text)

Autoimmune regulator (AIRE) deficiency in humans induces a life-threatening generalized autoimmune disease called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), and no curative treatments are available. Several models of AIRE-deficient mice have been generated, and although they have been useful in understanding the role of AIRE in central tolerance, they do not reproduce accurately the APECED symptoms, and thus there is still a need for an animal model displaying APECED-like disease. We assessed, in this study, the potential of the rat as an accurate model for APECED. In this study, we demonstrate that in rat, AIRE is expressed by MHC class II (MCH-II)+ and MHC-II- medullary thymic epithelial cells in thymus and by CD4int conventional dendritic cells in periphery. To our knowledge, we generated the first AIRE-deficient rat model using zinc-finger nucleases and demonstrated that they display several of the key symptoms of APECED disease, including alopecia, skin depigmentation, and nail dystrophy, independently of the genetic background. We observed severe autoimmune lesions in a large spectrum of organs, in particular in the pancreas, and identified several autoantibodies in organs and cytokines such as type I IFNs and IL-17 at levels similar to APECED. Finally, we demonstrated a biased Ab response to IgG1, IgM, and IgA isotypes. Altogether, our data demonstrate that AIRE-deficient rat is a relevant APECED animal model, opening new opportunity to test curative therapeutic treatments.



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Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AireRatabnormal NK cell number  IMP  RGD 
Aireem1AngRatabnormal NK cell number  IMP  RGD 
BN-Aireem1Ang-/-Ratabnormal NK cell number  IMP  RGD 
AireRatabnormal thymus morphology  IMP  RGD 
Aireem1AngRatabnormal thymus morphology  IMP  RGD 
BN-Aireem1Ang-/-Ratabnormal thymus morphology  IMP  RGD 
AireRatalopecia  IMP  RGD 
Aireem1AngRatalopecia  IMP  RGD 
BN-Aireem1Ang-/-Ratalopecia  IMP  RGD 
SD.BN-Aireem1Ang-/-Ratalopecia  IMP  RGD 
AireRatdecreased circulating creatinine level  IMP  RGD 
Aireem1AngRatdecreased circulating creatinine level  IMP  RGD 
BN-Aireem1Ang-/-Ratdecreased circulating creatinine level  IMP  RGD 
AireRatdecreased skin pigmentation  IMP  RGD 
Aireem1AngRatdecreased skin pigmentation  IMP  RGD 
BN-Aireem1Ang-/-Ratdecreased skin pigmentation  IMP  RGD 
SD.BN-Aireem1Ang-/-Ratdecreased skin pigmentation  IMP  RGD 
AireRatincreased autoantibody level  IMP  RGD 
Aireem1AngRatincreased autoantibody level  IMP  RGD 
BN-Aireem1Ang-/-Ratincreased autoantibody level  IMP  RGD 
AireRatincreased autopod size  IMP  RGD 
Aireem1AngRatincreased autopod size  IMP  RGD 
BN-Aireem1Ang-/-Ratincreased autopod size  IMP  RGD 
SD.BN-Aireem1Ang-/-Ratincreased autopod size  IMP  RGD 
AireRatnail dystrophy  IMP  RGD 
Aireem1AngRatnail dystrophy  IMP  RGD 
BN-Aireem1Ang-/-Ratnail dystrophy  IMP  RGD 
SD.BN-Aireem1Ang-/-Ratnail dystrophy  IMP  RGD 
AireRatvariable depigmentation  IMP  RGD 
Aireem1AngRatvariable depigmentation  IMP  RGD 
BN-Aireem1Ang-/-Ratvariable depigmentation  IMP  RGD 
SD.BN-Aireem1Ang-/-Ratvariable depigmentation  IMP  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Aire  (autoimmune regulator)
Aireem1Ang  (autoimmune regulator; ZFN induced mutant1, Ang)

Genes (Mus musculus)
Aire  (autoimmune regulator)

Genes (Homo sapiens)
AIRE  (autoimmune regulator)


Additional Information